Nephroprotective Effect of Garcinia Pedunculata Fruit Extract on Gentamicin Induced Neprotoxicity in Rats

AIM: Nephrotoxicity is one of the most common kidney problems and occurs when body is exposed to drug or toxin. A number of therapeutic agents can adversely affect the kidney resulting in acute renal failure, chronic interstitial nephritis, and nephritic syndrome because increasing number of potent therapeutic drugs like aminoglycoside antibiotics, chemotherapeutic agents and NSAIDS. Nephroprotective agents are the substances which possess protective activity against nephrotoxicity. Medicinal plants like Garciniapedunculatatraditionally use to protect nephrotoxicity by boiling three to four pieces of dried fruit pulp of the plants and taken it after cooling it. Thus in this study i have plan to use the dried fruit pulp of Garciniciapedunculatawhich possess nephroprotective activity on Gentamicin induced nephrotoxicity. DISCUSSION: Acute toxicity study: Herbal products prepared from various medicinical plants have become famous in health care and obtained from natural sources. [6] It is well known known that the herbal medicines contain more than one plant or active constituents and their therapeutic efficacy is not provided by a single group of compounds. Some of these impound act synergistically to modify the bioavailability and efficacy of active constituent [3]. The bioactive compound from the medicinal are concluded to be safe without knowing the possible health care benefits and thus commonly used as self medication. However, there is a defect on toxicological data of these compounds. So, acute toxicity study is required to identify the range of doses and probable clinical signs evoked by the test impound in animal under investigation. Moreover, it is a tool for calculating therapeutic index of a lead compound. The present study reveals the acute toxicity of Garcinia pedunculata fruit extract. No morbidity and mortality were observed at a higher dose of2000 mg/kg throughout the 14 days observation period. This acute study helps to predict that it does not contain any type of toxicity and it it full safe. Experimental induction of gentamicin and their treatment with the extract: Nephrotoxicity is an undesired side effect of chemotherapy in general. Most chemotherapy drugs target pathways that are essential to dividing cells[27]. Several studies have now documented the importance of reactive oxygen metabolites in gentamicin induced renal damage[28]. Nephrotoxicity of the drugs is usually associated with their accumulation in renal cortex, dependent upon their affinity to kidneys and on kinetics of drug trapping process[27]. The nephrotoxicity of aminoglycosideantibiotics, and specially that of the most commonly used compound, gentamicin is well documented[30,31]. Several studies have reported that oxygen free radical are considered to be important mediators of gentamicin induced renal failure. Gentamicin induced nephroxicity is characterized by elevated levels of urea, creatinine, uric acid, total protein sodium and potassium in serum as well as urine urea and creatinine, severe proximal tubularnecrosis, renal failure were found to be significantly increased in rats treated with only gentamicin. Similar pattern of changes were also observed in this study following gentamicin treatment. GP supplemation to GM treated rats recorded decrement in levels of urea, creatinine, uric acid, total protein, sodium and potassium in serum and also in urine urea and creatinine. These observations indicate an improved in renal function. GM administration to control rats produced a typical pattern of nephrotoxicity which was manifestated by marked increase in serum BUN. GP supplementations to GM treated rats recorded decrement in levels of blood urea nitrogen in plasma. Histopathological results demonstrating structural changes n renal tissue of aminoglycoside antibiotics such as GM were reported by some researches[31]. Histopathological view of renal sections in GM treated groups showed the degeneration, desquamation and necrosis in tubules, blood vessel congestion and swelling in glomerulus, as compared to control groups. Groups treated with GM + GP 200 mg/ kg showed tubular necrosis, necrotic changes, karyopicnosis, glomeruli showed mesangeal matrix expansion. Glomerular and tubular epithelial changes were considerably mild in groups treated with GM + 400 mg/kg and GM + 600 mg/kg i.e animal treated with GP 400 mg/kg showed mild glomerular mesangeal matrix expansion, mild tubular epithelial changes and no congestion in blood vessels while in case of animal treated with GP 600 mg/kg showed regeneration in tubular epithelial cells. Thus, morphological changes in kidneys were because of GM administration, but these changes tended to be mild in GM + GP treatment.CONCLUSION: In conclusion, gentamicin treatment resulted in impairments of renal function markers, and histopathological changes in the kidneys of rats.Co-administration of GM with GP lessened the negative effects of GM- induced nephrotoxicity and significant decrease of all the parameters in gentamicin treated rats. The beneficial effects of Garciniapedunculatamay be attributed to the amelioration of renal function.Thus the result showed that the ethanolic fruit extract of Garciniapedunculataoffer protection against the damaging renal side effects of gentamicin. Further investigation of these promising protective effects of Garciniapedunculatafruit extract against gentamicin- induced renal injury may have a considerable impact on developing clinically feasible strategies to treat patients with renal failure.