the occasional use of pesticides in large amounts may cause environmental pollution and therefore be a cause of concern .
residual amounts of organochlorine and organophosphate pesticides have been detected in soil , water reservoirs , vegetables , grains and other food products .
organophosphates induce toxicity in mammals through inhibition of acetylcholinesterase ( ache ) and subsequent activation of cholinergic receptors .
oxidative stress as a result of organophosphate exposure has been reported , and lipid peroxidation has been revealed to be one of the molecular mechanisms in organophosphate - induced toxicity [ 4 , 5 ] .
the use of natural remedies has been recently observed to be a good means of curbing oxidative stress by boosting the natural antioxidant defence system . in africa
, medicinal plants are used traditionally to treat various ailments . among the promising medicinal plants , ziziphus mucronata(zm ) in the family ramnaceae
various parts of the tree are already in use by common people as medicine and as food .
the roots , bark and leaves are used in the treatment of arthritis , chest pains and boils .
the sweet fruits of the plant are widely eaten in botswana , and they are dried , ground to powder and cooked as porridge . in botswana ,
a proposal has been made that the fruit might be useful in protecting the population from being affected by dimethoate toxicity .
hence , the present study has been aimed at establishing the antioxidant and hepatoprotective properties of zm fruit extracts .
other chemicals were of analytical grade and were bought from sigma - aldrich ( st .
the dried fruits were ground with a laboratory grinder to obtain 500 g of powder .
the powder was soaked and extracted in hexane , 50% hexane / chloroform , chloroform , 50% chloroform / methanol , methanol and 70% methanol / water for 24 hr .
thirty male sprague dawley ( sd ) albino rats aged 20 - 21 weeks were kept in galvanized cages under a controlled temperature of 25 and a normal photoperiod ( 12-h dark , 12-h light ) .
the animals were fed commercial food pellets ( protein : 18% , fat : 6% , fiber : 6% , carbohydrates : 56% , calcium : 0.6% moisture : 10% ) and water ad libitum .
all procedures with the animals were performed in accordance with the protocols established by the university of botswana animal care committee ( approval no : ub / irb/1084 ) .
the thirty adult male rats were divided into six groups of 5 rats each and treated as follows : group 1 - normal control ( nc ) received distilled water , group 2 - dimethoate control ( dc ) received 6 mg / kg.bw.day dimethoate dissolved in distilled water , group 3 - experimental group ( e1 ) received dimethoate(6 mg / kg.bw ) + zmfm ( 100 mg / kg.bw ) , group 4 - experimental group ( e2 ) received dimethoate ( 6 mg / kg.bw ) + zmfm ( 200 mg / kg.bw ) , group 5 - experimental group ( e3 ) received dimethoate ( 6 mg / kg.bw ) + zmfm ( 300 mg / kg.bw ) , group 6 - experimental control ( eo ) received zmfm ( 300 mg / kg.bw ) only .
the experiment was run for 90 days , and all extracts were administered orally with the help of a rubber tube and syringe . at the end of the experiment , rats were sacrificed after having been treated with mild ether anaesthesia .
blood was collected in heparinized tubes and centrifuged at a rate of 6000 rotations per minute , after which plasma samples were drawn and stored at -70 for further analysis .
the rat liver tissue was removed and immediately fixed in 10% phosphate - buffered formalin for 24 hr .
the tissue was dehydrated in an ethanol series ( 70% , 80% , 100% , and 100% ) , cleared in xylene and embedded in paraffin .
five--thick sections were taken by using a rotary microtone , and sections were affixed on clean glass slides by gentle heating .
the sections were deparaffinised , stained with haematoxylin and eosin , and mounted with a cover slip by using neutral mounting media ( dpx ) .
the 2 , 2-diphenyl-1-picryl hydrazyl radical ( dpph ) semiquantitative assay was performed on thin layer chromatography according to the method described by yeboah and majinda , and the spectrophotometric measurement of free - radical scavenging activities of the extracts by dpph was done using the method described by stoilova et al . .
( abts ) was determined as described by pellegrini et al . , and the total phenol content ( tpc ) was determined by using the method described by stoilova et al . .
activities of serum glutamate oxaloacetate transaminase ( sgot ) , serum glutamate pyruvate transaminase ( sgpt ) and alkaline phosphatase ( alp ) and measurements of the levels of plasma low - density lipoproteins ( ldl ) , highdensity lipoproteins ( hdl ) , total protein ( tp ) , triglyceride ( tg ) and cholinesterase activity were done using kits from aggape diagnostics , india .
thiobarbaturic acid reactive substances ( tbars ) were measured by using the method described by chaturvedi , and reduced glutathione ( gsh ) was measured by using the method described by ellman .
vitamin c was estimated according to the method described by omaye et al . , and
superoxide dismutase ( sod ) was estimated according to flohe and otting , and the activity of catalase was assayed by using the method described by bisswanger .
the total phenol content was estimated by using a linear regression on the standard curve of the standard ( gallic acid ) .
various concentrations ( 0.1  , 0.5 ,1.0  , 5.0  , and 10.0  ) of the fruit extracts from different solvents spotted on the tlc sheet showed high activity as indicated by the yellow color over the purple dpph background .
extracts from 100% methanol , 70% methanol / water , 70% methanol / chloroform,100%chloroform,50% hexane / chloroform and 100% hexane changed to yellow on the purple dpph background .
the extent of yellow coloration was comparable to the gallic acid standard ( fig 1 ) .
the percentage inhibition increased when going from low - polarity - solvent to a high - polarity - solvent extracts : namely , 100% methanol , 70% methanol/ chloroform , 100% chloroform , 50% hexane / chloroform , 100% hexane in that order .
the standards , gallic acid , displayed 100% dpph inhibition ( fig 2 ) . as presented in table 1 , the phenol content was found to increase from 30 mg gae / g for hexane extract to 100 mg gae / g for 50% methanol chloroform , 57 mg gae / g for chloroform , 48 mg gae / g for 50% hexane / chloroform and 250 mg gae / g for 70% methanol extract . * values are numbers or means  sds .
effect of abts free radical scavenging activity of z. mucronata was assayed at various concentrations from 2.5 , 5 , 10 , 25 , 50 and 100 /. the method is based on the ability of antioxidant molecules to quench the long lived abts radical cation ( abts ) .
significant abts scavenging activity was evident in 100% methanol extract 7.21 , and a weak scavenging activity was observed in 100% hexane ( table 2 ) .
extracts were tested at 2.5 , 5 , 10 , 25 , 50 and 100 /. reference standard ( gallic acid ) was tested at 1 , 2 , 4 , 8 and 16 /. daily administration of dimethoate resulted in elevated levels of tbars in the plasma of the dc group .
a dosedependent reduction in the levels of plasma tbars was associated with the zmfm administration .
compared with the levels in nc rats , liver transaminases , serum glutamate oxaloacetate transaminase ( sgot ) , serum glutamate pyruvate transaminase ( sgpt ) and alkaline phosphatase ( alp ) were increased significantly ( p < 0.001 ) in rats of the dc group .
significant dose - dependent declines in the levels of malonyldialdihyde and the activities of tranaminases were observed in plasma sgot ( p < 0.001 ) , sgpt ( p < 0.001 ) and alp ( p <
administration of zmfm only resulted in no signs of toxicity as evidenced by the levels of tbars having no significant differences from those of the nc group .
sgot , sgpt and alp also had no significant differences when compared to the values for the nc group ( table 3 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and ( p < 0.05,p < 0.001 ) compared with dimethoate control ( dc ) .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , e3 ( 300 mg / kg.bw + dm ) , and eo ( 300 mg / kg.bw ) .
the results showed that the plasma levels of reduced gsh , vitamin c and e were reduced significantly ( p < 0.001 ) in dc rats compared to the levels in nc rats .
when compared with nc rats , the levels were also reduced significantly ( p < 0.001 ) in experimental rats ( e1-e3 ) in a dose - dependent manner .
although the activity of sod was low in the e3 group , it still differed significantly from levels in the dc group ( p < 0.05 ) .
the activities of catalase in the e3 group differed significantly from those in the dc group , but no difference was noted when comparison was made with the nc group .
administration of zmfm along with dimethoate helped the animals to ameliorate the levels of these non - enzymatic antioxidants ( table 4 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
the results showed that the activities of sod and catalase were enhanced significantly ( p < 0.05 ) in dc rats as compared to nc rats , and significant decreases in the activities of sod and catalase were noticed in the experimental groups and were dose dependent . the highest significant reductions ( p < 0.05 for sod and p < 0.001 ) for catalase were noticed in the e3 group when compared to the dc group . the sod and the catalase in the e3 group showed significant differences from the values for both the dc group and the nc group ( p < 0.05 ) ( table 5 ) .
values are expressed as means  sems , n = 5 for each treatment ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and ( p < 0.05,p < 0.001 ) compared with dimethoate control ( dc ) .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
dimethoate administration was shown to significantly lower hdl levels ( p < 0.001 ) and total protein ( p
zmfm administration along with dimethoate successfully restored the hdl levels in the e2 and the e3 groups , and they differed significantly ( p < 0.05 ) from the dc group . on the other hand , dimethoate significantly increased the levels of low - density lipoprotein , cholesterol and triglyceride ( p < 0.001 ) as compared to the levels in the nc group .
the ldl , cholesterol , triglyceride ( p < 0.001 ) and total protein ( p < 0.05 ) levels were found to decline significantly in the e3 group as compared to the dc group .
levels of total protein and triglyceride differed significantly from those in the nc group , as did the levels ldl and cholesterol ( p < 0.05 ) . in the e2 group ,
a decline was noticed , and it showed a significant difference from the nc group .
a similar response was noted for the e1group , but the changes were less significant than they were for the e2 group ( table 6 ) .
values are expressed as means  sems , n = 5 for each treatment ( p < 0.05*,p < 0.001 * * ) compared with normal control and ( p < 0.05,p
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
the cholinesterase activity declined ( p < 0.005 ) in dimethoate - treated rats when compared to the normal control rats .
there was a gradual and significant ( p < 0.005 ) increase in the cholinesterase activity during zmfm administration .
the increment in cholinesterase activity occurred as a result of increasing zmfm dosage ( table 7 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control and ( p < 0.05,p < 0.001 ) compared with dimethoate control .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw +
zmfm administration revealed a preventive effect on the hepatocytes when compared to the dimethoate control ( dc ) .
the dc control group showed evident hepatic damage as shown by widening sinusoids , loss of both hepatocellular membrane and hepatocytes when compared to the normal control group .
the preventive effect was shown by reduced necrosis in zmfm - fed rats when compared to dimethoate - fed rats ( fig 3 ) .
( a ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver of the nc group .
( b ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver of dc group .
( c ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed livers of the e1 group .
( d ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver in the e2 group .
most tissue was well preserved with no massive fatty changes , necrosis , and sinusoids not too wide , almost resembling the normal hepatocytes of the normal control .
( e ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed livers of the e3 group .
the hepatocytes are well preserved with no distinguishable damage to the cell membranes ( x400 ) .
various concentrations ( 0.1  , 0.5 ,1.0  , 5.0  , and 10.0  ) of the fruit extracts from different solvents spotted on the tlc sheet showed high activity as indicated by the yellow color over the purple dpph background .
extracts from 100% methanol , 70% methanol / water , 70% methanol / chloroform,100%chloroform,50% hexane / chloroform and 100% hexane changed to yellow on the purple dpph background .
the extent of yellow coloration was comparable to the gallic acid standard ( fig 1 ) .
zm fruit extracts showed high antioxidant activity . the increase in the antioxidant activity occurred in a concentration - dependent manner
the percentage inhibition increased when going from low - polarity - solvent to a high - polarity - solvent extracts : namely , 100% methanol , 70% methanol/ chloroform , 100% chloroform , 50% hexane / chloroform , 100% hexane in that order .
as presented in table 1 , the phenol content was found to increase from 30 mg gae / g for hexane extract to 100 mg gae / g for 50% methanol chloroform , 57 mg gae / g for chloroform , 48 mg gae / g for 50% hexane / chloroform and 250 mg gae / g for 70% methanol extract .
effect of abts free radical scavenging activity of z. mucronata was assayed at various concentrations from 2.5 , 5 , 10 , 25 , 50 and 100 /. the method is based on the ability of antioxidant molecules to quench the long lived abts radical cation ( abts ) .
significant abts scavenging activity was evident in 100% methanol extract 7.21 , and a weak scavenging activity was observed in 100% hexane ( table 2 ) .
extracts were tested at 2.5 , 5 , 10 , 25 , 50 and 100 /. reference standard ( gallic acid ) was tested at 1 , 2 , 4 , 8 and 16 /.
daily administration of dimethoate resulted in elevated levels of tbars in the plasma of the dc group .
a dosedependent reduction in the levels of plasma tbars was associated with the zmfm administration .
compared with the levels in nc rats , liver transaminases , serum glutamate oxaloacetate transaminase ( sgot ) , serum glutamate pyruvate transaminase ( sgpt ) and alkaline phosphatase ( alp ) were increased significantly ( p < 0.001 ) in rats of the dc group .
significant dose - dependent declines in the levels of malonyldialdihyde and the activities of tranaminases were observed in plasma sgot ( p < 0.001 ) , sgpt ( p < 0.001 ) and alp ( p <
administration of zmfm only resulted in no signs of toxicity as evidenced by the levels of tbars having no significant differences from those of the nc group .
sgot , sgpt and alp also had no significant differences when compared to the values for the nc group ( table 3 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and ( p <
0.05,p < 0.001 ) compared with dimethoate control ( dc ) . e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , e3 ( 300 mg / kg.bw + dm ) , and eo ( 300 mg / kg.bw ) .
the results showed that the plasma levels of reduced gsh , vitamin c and e were reduced significantly ( p < 0.001 ) in dc rats compared to the levels in nc rats .
when compared with nc rats , the levels were also reduced significantly ( p < 0.001 ) in experimental rats ( e1-e3 ) in a dose - dependent manner .
although the activity of sod was low in the e3 group , it still differed significantly from levels in the dc group ( p < 0.05 ) .
the activities of catalase in the e3 group differed significantly from those in the dc group , but no difference was noted when comparison was made with the nc group .
administration of zmfm along with dimethoate helped the animals to ameliorate the levels of these non - enzymatic antioxidants ( table 4 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and ( p < 0.05,p <
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
the results showed that the activities of sod and catalase were enhanced significantly ( p < 0.05 ) in dc rats as compared to nc rats , and significant decreases in the activities of sod and catalase were noticed in the experimental groups and were dose dependent . the highest significant reductions ( p < 0.05 for sod and p < 0.001 ) for catalase were noticed in the e3 group when compared to the dc group . the sod and the catalase in the e3 group showed significant differences from the values for both the dc group and the nc group ( p < 0.05 ) ( table 5 ) .
values are expressed as means  sems , n = 5 for each treatment ( p < 0.05*,p < 0.001 * * ) compared with normal control ( nc ) and ( p < 0.05,p < 0.001 ) compared with dimethoate control ( dc ) .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
dimethoate administration was shown to significantly lower hdl levels ( p < 0.001 ) and total protein ( p < 0.001 ) in the dc group . zmfm administration along with dimethoate successfully restored the hdl levels in the e2 and the e3 groups , and they differed significantly ( p < 0.05 ) from the dc group . on the other hand , dimethoate significantly increased the levels of low - density lipoprotein , cholesterol and triglyceride ( p < 0.001 ) as compared to the levels in the nc group . the ldl , cholesterol , triglyceride ( p < 0.001 ) and total protein ( p < 0.05 ) levels were found to decline significantly in the e3 group as compared to the dc group .
levels of total protein and triglyceride differed significantly from those in the nc group , as did the levels ldl and cholesterol ( p < 0.05 ) . in the e2 group ,
a decline was noticed , and it showed a significant difference from the nc group .
a similar response was noted for the e1group , but the changes were less significant than they were for the e2 group ( table 6 ) .
values are expressed as means  sems , n = 5 for each treatment ( p < 0.05*,p < 0.001 * * ) compared with normal control and ( p < 0.05,p < 0.001 ) when compared with dimethoate control .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw + dm ) .
the cholinesterase activity declined ( p < 0.005 ) in dimethoate - treated rats when compared to the normal control rats .
there was a gradual and significant ( p < 0.005 ) increase in the cholinesterase activity during zmfm administration .
the increment in cholinesterase activity occurred as a result of increasing zmfm dosage ( table 7 ) .
values are expressed as means  sems , n = 5 for each treatment , ( p < 0.05*,p < 0.001 * * ) compared with normal control and ( p < 0.05,p < 0.001 ) compared with dimethoate control .
e1 ( 100 mg / kg.bw + dm ) , e2 ( 200 mg/ kg.bw extract + dm ) , and e3 ( 300 mg / kg.bw +
zmfm administration revealed a preventive effect on the hepatocytes when compared to the dimethoate control ( dc ) .
the dc control group showed evident hepatic damage as shown by widening sinusoids , loss of both hepatocellular membrane and hepatocytes when compared to the normal control group .
the preventive effect was shown by reduced necrosis in zmfm - fed rats when compared to dimethoate - fed rats ( fig 3 ) .
( a ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver of the nc group .
( b ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver of dc group .
( c ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed livers of the e1 group .
( d ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed liver in the e2 group .
most tissue was well preserved with no massive fatty changes , necrosis , and sinusoids not too wide , almost resembling the normal hepatocytes of the normal control .
( e ) light microphotograph of haematoxylin and eosin - stained and formalin - fixed livers of the e3 group .
the hepatocytes are well preserved with no distinguishable damage to the cell membranes ( x400 ) .
exposure to various organic compounds including a number of environmental pollutants and drugs can cause cellular damages through metabolic activation of those compounds by highly reactive substances such as reactive oxygen species ( ros ) [ 17 , 18 ] .
dimethoate is one of the organophosphates frequently used in agriculture , and it has been reported to generate oxidative stress and impose toxicity .
organophosphates have been found to inhibit cholinesterase ( ache ) and subsequent activation of cholinergic receptors .
the use of antioxidants like botanicals is an effective means to fight against the deleterious effects of oxidative stress .
botanicals are natural sources of antioxidants because of their richness in phenol , flavonoids and other anti - oxidants . in the present study ,
various extracts of zm were found to contain significant amounts of phenols . in the present study ,
the total phenol content was seen to increase when going from the less polar solvent extracts to the more polar solvent extracts .the highest concentration was present in the 70% methanol / water extract .
zm fruit extracts exhibited high antioxidant activity on the tlc / dpph antioxidant assay ( fig 1 ) .
the tlc - dpph assay was confirmed by the dpph spectrophotometric assay(fig 2 ) and abts ( table2 ) assays .
the methanol fruit extract had the highest dpph scavenging activity ( 96 shown % ) and exhibited 7.21/-inhibiting concentration ( ic50 ) on abts other solvents showed lower antioxidant activities ; hence , the highest antioxidant activity by the methanol extracts best represents the fruits antioxidant potential .
it accumulates acetylcholine and prevents the smooth transmission of nerve functions , leading to convulsions and death .
dimethoate inhibits the activity of the enzyme cholinesterase that hydrolyses acytylcholine into acetyl and choline and , hence , prevents the return of cholinergic neurons to normal .
the liver is the primary organ involved in xenobiotic metabolism and is a major target organ for chemicals and drugs . in the present study , oral administration of dimethoate to rats
caused hepatic damage , as evidenced by the elevations in the hepatospecific enzyme activities , as well as by the severe alterations in different liver marker parameters .
tbars , sgot , sgpt and alp were significantly increased ( p < 0.05 ) in the dimethoate control ( dc ) group .
administration of zmfm ( table3 ) significantly ( p < 0.005 ) lowered the levels of tbars , sgot , sgpt , and alp when coupled with dimethoate during its administration , thus demonstrating a dose - dependent preventive effect of the extract .
the levels of gsh , vitamin c and vitamin e were observed to decline ( p < 0.05 ) in dimethoate - treated rats .
administration of the zmfm ( table4 ) resulted in a gradual recovery of the non - enzymatic antioxidants in a dose - dependent manner .
glutathione is important in neutralizing the reactive intermediates and radical species generated during oxidative stress .
the depletion of gsh may be a result of its being used up in quenching omethoate radicals .
an oral feeding of the extract seems to scavenge free radicals or interfere with free radical formation in vivo .
administration of the extract is , thus , demonstrated to prevent gsh depletion , hence leading to normal gsh production .
vitamin e is thought to be an important chain - breaking antioxidant , is the major soluble antioxidant in all cellular membranes , and protects against lipid peroxidation .
zmfm may possibly play a role in scavenging the reactive oxygen species ( ros ) .
this thus allows the recovery of vitamin e which was used up in scavenging dimethoateinduced radicals .
the observed significant ( p < 0.05 ) decline in the activity of sod in the experimental groups was possibly a result of the extracts that were administered to the rats .
this decrease may be a possible indication that the extracts alleviate dimethoate effects on progenitor cells and possibly reduce the activation of compensatory mechanisms .
this may possibly occur when the zm extract scavenges the free radicals produced as a result of dimethoate administration .
the preventive effect may also occur through the blockage of the mechanisms leading to biotransformation of dimethoate to its destructive oxygen analogue ( omethoate ) .
the observed elevated catalase activity may be a result of an adaptive response to the generated free radicals .
this directly indicates the failure of the total antioxidant defense system as shown by lipid peroxidation .
the superoxide ion generated is , therefore , accounted for by the enhanced sod and is converted to h2 o2 or glutathione peroxidase .
a decrease in the catalase activity suggests the possibility that zmfm scavenges the free radicals before they necessitate a natural adaptive response by the enzyme .
the study , thus suggests the ability of zmfm to alleviate dimethoate - induced oxidative stress .
elevated low - density lipoprotein ( ldl ) , cholesterol ( cho ) and triglyceride ( trig ) levels and decreased high - density lipoprotein ( hdl ) and total protein levels were observed in dimethoate - treated rats , when compared to normal control rats , after 90 days of treatment .
administration of zmfm extract resulted in significant ( p < 0.05 ) suppressions in ldl , cho and trig levels when compared to normal control rats .
the extracts brought about significant ( p < 0.005 ) increases in the hdl and the total proteins levels when compared to the dimethoate control group .
the increases in the total protein and hdl levels in the extract - treated rats possibly suggests the ability of the extracts to slow down dimethoate - damaging effects on the liver .
ldls are known to carry cholesterol to the peripheral tissues where it can be deposited and increase the risk of atherosclerotic attack and peripheral vascular disease .
the orally - administered extract offers more benefits by increasing the level of hdls in rat plasma . unlike the ldls ,
hdls hasten the removal of cholesterol from peripheral tissues to the liver for catabolism and excretion [ 1 , 25 ] .
the histological studies of the liver sections presented in fig 3provide supportive evidence for the protective effects of zmfm .
the liver sections of normal control animals showed normal hepatic cells , each with preserved and prominent hepatocytes .
the liver sections of dimethoateintoxicated rats showed loss of hepatocytes and loss of cellular boundaries and widened sinusoids ; zmfm attenuated the degenerative effects of dimethoate toxicity .
this was observed in the reduced intensity in liver - tissue degenerative changes . here ,
less necrosis , limited loss of cell boundaries and reduced loss of intact hepatocytes were observed .
in conclusion , zmfm extract could protect against oxidative stress by decreasing lipid peroxidation and enhancing the effects of enzymatic and non - enzymatic antioxidants .
 objective : the study was carried out to evaluate the hepatoprotective and antioxidant potential of ziziphus mucronata ( zm ) fruit extract.methods:the different types of fruit extract were prepared by soaking the dry powdered fruit in different solvents followed by rotary evaporation . each extract was tested for its phenol content and antioxidant activities . 
 an in vivo study was performed in sprague- dawley ( sd ) rats . 
 thirty adult male sd rats ( aged 21 weeks ) were divided into six groups of five rats each and treated as follows : the normal control ( nc ) received distilled water while the dimethoate control ( dc ) received 6 mg / kg.bw.day-1 dimethoate dissolved in distilled water . 
 the experimental groups e1 , e2 , e3 , and e0 received dimethoate ( 6 mg / kg.bw ) + zmfm ( 100 mg / kg.bw-1 ) , dimethoate ( 6 mg / kg.bw ) + zmfm ( 200 mg / kg.bw-1 ) , dimethoate ( 6 mg / kg.bw ) + zmfm ( 300 mg / kg.bw-1 ) , and zmfm ( 300 mg / kg.bw-1 ) only . both the normal control and the dimethoate control groups were used to compare the results . 
 after 90 days , rats were sacrificed , blood was collected for biochemical assays , and livers were harvested for histological study.results:high phenol content was estimated , and 2 , 2- diphenyl-1-picryl hydrazyl radical ( dpph ) spectrophotometric , thin layer chromatography ( tlc ) and 2 , 2-azobis-3-ethyl benzothiazoline-6-sulphonic acid ( abts ) assays showed a high antioxidant activity among the extracts . 
 the preventive effects observed in the e1 , e2 and e3 groups proved that the extract could prevent dimethoate toxicity by maintaining normal reduced glutathione ( gsh ) , vitamin c and e , superoxide dismutase , catalase , cholineasterase and lipid profiles . 
 the preventive effect was observed to be dose dependent . 
 the eo group showed no extractinduced toxicity . 
 histological observations agreed with the results obtained in the biochemical studies.conclusion:the study demonstrated that zm methanol fruit extract is capable of attenuating dimethoate - induced toxicity because of its high antioxidant activity . 