# Atrazine-Induced Hepato-Renal Toxicity in Adult Male Xenopus laevis Frogs
## 4 Discussion  
The results have revealed the hepato-renal cytotoxicity of sub-chronic exposure to the pesticide atrazine in adult _Xenopus_ frogs. Interestingly, the various doses of atrazine used showed variable significant levels of toxicity in the liver and kidneys, suggesting that, though this pesticide may be useful to increased agricultural productivity, caution must be applied in its application. The significantly elevated serum MDA (500 ug/L exposed group) corroborates previous reports of elevated MDA in the liver, gills and muscles of bullfrog tadpoles [41] and in rats [25; 42] exposed to atrazine. Correspondingly, the presence of hepatic cell injury with consequent functional implications is predicated on the significant increases in serum levels of ALT in the 200 ug/L and 500 ug/L exposure groups, as ALT levels function in the maintenance of cell membrane integrity [25; 43]. However, the mildly reduced MDA level following 200 ug/L sub-chronic exposure suggests homeostatic adjustment adaptation in this group, as well as minimal adverse effects resulting from the non-significantly increased serum levels of AST and ALKp in all the treated groups, signifying the variable atrazine effects. This study utilized the sensitive high-performance liquid chromatography method, ensuring the accuracy of the measurements. The serum levels of ALT, AST and ALKp are markers of cell membrane integrity [26; 43]. These results suggest hepatotoxicity and therefore disturbances of liver function following ATZ exposure. Additionally, the assessment of renal function is based on the serum levels of urea and creatinine as biomarkers above or below the normal physiological level. Therefore, the non-significantly increased urea levels in all exposure groups and the significantly elevated creatinine levels in the 200 ug/L and 500 u/L treated groups relative to the control group suggest renal glomeruli filtration dysfunction and/or impairment in all the treated groups but more severely in the 200 ug/L and 500 u/L atrazine-exposed groups. The observed general trend in serum creatinine levels with a concentration-dependent effect in atrazine exposure suggests a greater adverse effect relative to urea as a renal biomarker. Histopathology observations of hepatocyte perturbations are similar to reports observed in other atrazine-exposed species [44; 45]. Atrazine-induced histological alteration is initiated by hypertrophy, as observed in the 200 ug/L and 500 ug/L exposed groups, as was previously reported [46] and which has been suggested to be an adaptive response to atrazine exposure [47]. Hepatocyte vacuolization observed in all our atrazine-exposed groups, particularly the 200 ug/L and 500 ug/L cohorts, has been reported in fish [45] and mice with attendant effects in lipid metabolism. Additionally, the observed central vein and sinusoidal congestion in the 0.01 ug/L and 500 ug/L groups suggest obstruction by immune cell migration and cellular breakdown debris. This corroborates with observations of vascular hemorrhaging indicated by erythrocyte infiltration into the hepatocytes reported in frogs exposed to 500 ug/L of ATZ. The red blood cell (erythrocytes) extravasation suggests compromised sinusoidal endothelium and may be a consequence of increased intra-sinusoidal pressure arising from vascular congestion [48]. Additionally, atrazine-induced perturbations in the immunology of amphibians are widely reported [49; 50]. Similarly, the observed apoptosis of neutrophils and Kupffer cells confirmed by the expression of caspase-3 in the liver of atrazine-treated groups suggests the potential for atrazine to suppress phagocytic process or action and the gathering of monocytes directly or indirectly to sites of inflammation through induction of apoptosis in the immune cells. Contrastingly, a significant decrease in the population of MMCs observed in all the ATZ-exposed groups correlates with a field study report of aggregated melanomacrophages in the livers of _L pipiens_ exposed to atrazine [51].