Nephrotoxicity In Wistar Rats Research Articles

Extracts from Commelina diffusa Protect Against Gentamicin-Induced Nephrotoxicity in Wistar Rats

Extracts from Commelina diffusa Protect Against Gentamicin-Induced Nephrotoxicity in Wistar Rats

Protective effect of Carica papaya leaf extract against mercuric chloride-induced nephrotoxicity in wistar rats

Introduction: Chronic kidney disease is the progressive loss of renal function, measured by creatinine, urea and proteinuria levels. Literatures show that renal damages can be ameliorated naturally by medicinal plants, one such plant is Carica papaya . Fresh leaves of C. papaya were collected, powdered, and extracted with ethanol to form ethanolic extract of C. papaya leaves (ECP). Aim and Objectives: The aim and objective of this study are to assess the remedial implications of ethanolic ECP leaves on mercuric chloride (HgCl2)-induced nephrotoxicity in female Wistar rats. The objectives of this study were to assess the effectiveness of two different oral doses of ECP using immunohistochemistry, histopathology, and serum biomarkers such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and semaphorin 3A. Materials and Methods: The rats were divided into five groups (n = 6): Control (Physiological saline, 2 ml/kg b. w), Negative control (HgCl2, 2.5 mg/kg b. w), Positive control (N-acetyl cysteine [NAC] 180 mg/kg b. w + HgCl2, 2.5 mg/kg b. w), Experimental group (C. papaya leaves, 300 and 600 mg/kg b. w + HgCl2, 2.5 mg/kg b. w) for 28 days orally through gavage. Collection of blood and renal tissue was done to determine the serum biomarkers, immunohistochemistry, and histopathology. Results: Pretreatment with 300 mg and 600 mg doses of ECP had protective effects slightly lower than NAC and equal to that of NAC on HgCl2-induced nephrotoxicity, respectively. Statistical analysis was performed using the one-way analysis of variance using SPSS version 17.0 with a statistical significance level of P

Ameliorative effect of a standardized polyherbal combination in methotrexate-induced nephrotoxicity in the rat

Context Nephrotoxicity is a renal dysfunction that arises from direct exposure to environmental chemicals or as a side effect of therapeutic drugs. Boerhaavia diffusa Linn. (Nyctaginaceae), Rheum emodi Wall. Ex. Meissn. (Polygonaceae), Nelumbo nucifera Gaertn. (Nelumbonaceae) and Crataeva nurvala Buch-Ham. (Capparidaceae) are well-recognized medicinal plants of Indian traditional system of medicine used for kidney disorders. Objectives The present investigation was undertaken to develop a chromatographically characterized polyherbal combination and to evaluate its nephroprotective activity. Materials and methods Roots of B. diffusa and R. emodi, flowers of N. nucifera and stem bark of C. nurvala were extracted by decoction using 70% ethanol. Response surface methodology (RSM) was used for the optimization of extraction parameters. Polyherbal combinations with different doses (150–300 mg/kg) were tested against methotrexate-induced nephrotoxicity in Wistar rats. Results The optimized extract contained 27% phenols and 15% flavonoids, which showed 75% 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging potential. Based on the retention time of high-performance liquid chromatography (HPLC) analysis, 17 out of 122 constituents were found common in all extracts and combinations. Two combinations showed significantly higher (p ≤ 0.05) DPPH scavenging potential and xanthine oxidase inhibition. The half maximal inhibitory concentration (IC50) of the best combination for DPPH scavenging and xanthine oxidase inhibition were 80 and 74 µg/mL, respectively. Treatment of methotrexate-induced nephrotoxic rats with polyherbal combination significantly (p ≤ 0.05) improved the kidney function markers, oxidative stress markers and histological parameters. Discussion and conclusion The developed combination was found to be effective in nephrotoxicity; it can be explored further for the management of drug-induced nephrotoxicity and other chronic kidney diseases.

NEPHROPROTECTIVE ACTIVITY OF PLUMERIA RUBRA AGAINST CISPLATIN INDUCED NEPHROTOXICITY IN EXPERIMENTAL RATS

Objective: The current study was designed to evaluate the protective effect of standardized hydroalcoholic extract of Plumeria rubra (HAEPR) against cisplatin-induced nephrotoxicity in Wistar rats. 
 Methods: HAEPR was administered orally at 3 dose levels (100,200,400 mg/kg). Vitamin E (250 mg/kg) was used as a Standard nephroprotective agent. The kidney function test (estimation of serum creatinine, albumin, blood urea nitrogen) oxidative stress study (estimation of superoxide dismutase, malondialdehyde activity) and histological examination of kidneys was conducted.
 Results: The efficacy of HAEPR was compared with Cisplatin (CP) treated group. Serum creatinine and BUN was significantly (p<0.01) elevated in CP-treated group compared to the control group. HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) decreased the serum creatinine and BUN levels. CP treated group exhibited significant (p<0.01) decrease in albumin when compared to control. Significant (p<0.01) increase in the serum albumin level was found in HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) compared to CP group. Significant (p<0.01) decrease in the activity of SOD was observed in the CP group as compared to control. HAEPR (100 and 200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) increased SOD levels. HAEPR (400 mg/kg) significantly (p<0.05) increased SOD levels. HAEPR (100,200,400 mg/kg) significantly (p<0.01) decreased MDA levels as compared to CP group. Histopathological examination of the kidneys showed that HAEPR markedly ameliorated Cisplatin-induced renal tubular necrosis. An extract was found effective at all doses, although low dose (100 mg/kg) was found to be more effective and comparable with the standard group (Vitamin E 250 mg/kg). 
 Conclusion: Present investigation revealed that HAEPR resulted in attenuation of Cisplatin-induced renal damage in rats.

Effect of Withania somnifera on gentamicin induced renal lesions in rats

Gentamicin induced renal complications are well known in humans and animals. Medicinal properties of Withania somnifera (L.) Dunal, Solanaceae, are recognized to improve renal functions. However, the pharmacological function of W. somnifera is not completely understood. We sought to unravel medicinal therapeutic function of W. somnifera on gentamicin-induced nephrotoxicity in wistar rats. Twenty-four adult male wistar rats evenly divided into four groups to evaluate in vivo nephroprotective and nephrocurative function of W. somnifera in gentamicin induced nephrotoxic rats. Experimental design as follows: Group I, saline control for 21 days; Group II, gentamicin nephrotoxic control for eight days; Group III, alcoholic extract of W. somnifera for 13 days+simultaneous administration of gentamicin and W. somnifera, from day 14 to 21 (nephroprotective) and Group IV, gentamicin for 8 days+alcoholic extract of W. somnifera from day 9 to 21 (nephrocurative). End of experiment, respective serum and kidney tissue samples used to analyze renal function. Withania somnifera as a nephroprotective and nephrocurative molecule significantly restore the renal function on gentamicin-induced nephrotoxicity. This phenomenon is accompanied with significantly reduced blood urea nitrogen, creatine, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein, calcium, potassium and kidney malondialdehyde concentrations. Additionally, W. somnifera significantly increased antioxidant activities of glutathione and superoxide dismutase to protect renal tissue damage from gentamicin in wistar rats. Over all, W. somnifera treated nephroprotective animal shows improved recovery compared to nephrocuartive. The nephroprotective or nephrocurative effect of W. somnifera could be due to inherent antioxidant and free-radical-scavenging principle(s). In the near future, biologically active compounds of W. somnifera (withanolides) could appear as a novel therapeutic molecule for renal disorders.

Evaluation of Chemical and Green Synthesized Iron Oxide Nanoparticles’ Associated Renal Toxicity in Different Experimental Models: A Comparative Study

Magnetic nanoparticles occupy a significant class of inorganic nanoparticles with its very promising application in biosensors and bio-imaging. Physical and chemical methods have been used conventionally to prepare magnetic nanoparticles. However, these methods have its own limitations, which redirected recent research towards safe, clean and eco-friendly green synthesis approach. In our study, green magnetic iron oxide nanoparticles (FeNP DG) were prepared by using aqueous Desmodium gangeticum root extract as a reducing as well as a capping agent. Nanoparticles used in different biological milieu has to be explored for their toxicity before its application. Thus prepared nanoparticles were evaluated for its nephrotoxicity in Wistar rats (100 mg/kg b.wt), in renal epithelial cells, LLC PK1 (1 mg/ml) and isolated mitochondria (0.25, 0.5, 1 mg/ml) and compared it with the conventionally prepared iron oxide nanoparticles (FeNP Chem). Our study demonstrate that chemically prepared FeNPs are toxic to kidney and its epithelial cells.On the other hand, when the same nanoparticles were prepared by green route (FeNP DG) exhibited minimum toxicity measured via the renal markers in blood and urine along with cytotoxicity assay in LLC PK1 cells. But at mitochondrial level, both FeNP Chem and FeNP DG were found to be toxic to the organelle.

Naringenin prevents doxorubicin-induced toxicity in kidney tissues by regulating the oxidative and inflammatory insult in Wistar rats

This study is undertaken to investigate the effects of naringenin on doxorubicin- (Dox) induced nephrotoxicity in Wistar rats. Dox 10 mg/kg body weight was administered intraperitoneally once and naringenin 50 and 100 mg/kg body weight was administered orally daily for 21 d. Dox-induced oxidative stress lead to steep elevation in blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), and kidney injury molecule-1 (KIM-1), compared to control, treatment with naringenin preserved kidney functions. With Dox treatment significant decrease in antioxidant enzymes with increase in malondialdehyde (MDA) compared to control was observed. Naringenin treatment reversed these values compared to Dox in kidney tissue. Dox treatment showed increased tissue nitric oxide levels naringenin treatment decreased nitric oxide (NO) in kidney tissue. Furthermore, Dox-induced inflammatory burst as indicated by up-regulation of nuclear factor-κB (NF-κB), tumour necrosis factor-α (TNF-α) tissue levels and prostaglandin-E2 (PGE-2). All such events were normalised back to normal by naringenin treatment.

Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats

Gentamicin is an aminoglycoside antibiotic widely used for the treatment of life-threatening infections caused by Gram-negative bacteria. The use of gentamicin was limited due to its ototoxic and nephrotoxic adverse effects. The current study was designed to evaluate the protective effect of ethyl acetate fraction from Rotula aquatica (EFRA) against gentamicin induced nephrotoxicity. The antioxidant enzymes status, lipid peroxidation, nitrate and ROS level, serum markers like creatinine, Urea, BUN were estimated in the present study. The histopathological analysis of renal tissues was done by H&E and PAS staining. The mRNA level expression of KIM-1, NF-κB, TNF- α, and IL-6 were measured by semi-quantitative reverse transcription-polymerase chain reaction. The changes in antioxidant parameters were restored by the treatment of EFRA at different dose (50 mg/kg bwt, 100 mg/kg bwt). The serum parameters, ROS, MDA and nitrate level were decreased by administration of EFRA. The EFRA ameliorates histological changes associated with gentamicin induced nephrotoxicity. The mRNA level expression of KIM-1, NF-κB, TNF- α, and IL-6 were downregulated in EFRA treated groups. The results from present study reveals the role of EFRA as good anti-inflammatory and nephro protective drug.

Nephroprotective Effect of Aqueous Extract of Pimpinella anisum in Gentamicin Induced Nephrotoxicity in Wistar Rats

Background: Pimpinella anisum known for its various medicinal properties is also a natural antioxidant and a free radical scavenger with no documented evidence as a nephroprotective agent. Objective: To evaluate the nephroprotective activity of aqueous extract of Pimpinella anisum seeds in a rodent model of gentamicin induced nephrotoxicity. Materials and Methods: Wistar albino rats of either sex, weighing 150–200 g was divided into 5 groups; normal saline, gentamicin 80mg/kg, intraperitoneally for 8 days, aqueous extract of Pimpinella anisum seeds at 1, 2, and 4g/kg, per oral for 8 days, the test extract administered 3 days prior and concurrently with gentamicin for 5 days. Blood urea, serum creatinine, uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed. Results: Gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea, serum uric acid, serum creatinine and blood urea nitrogen (107.5±16.92mg/dl, 0.8±0.09 mg/dl, 3.05±0.29 mg/dl, 47.8±9.07 mg/dl) respectively when compared to the saline treated groups. Co-administration of Pimpinella anisum extract with gentamicin decreased the rise in these parameters in a dose dependent manner. Histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats, whereas aqueous extract of Pimpinella anisum mitigated the severity of gentamicin-induced renal damage. Conclusion: To conclude, our data suggest that aqueous extract of Pimpinella anisum exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanism of action are warranted.

Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in Wistar rats through modulation of apoptotic pathway

In the present study, we have evaluated the nephroprotective effect of hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity model. Standardised extract was orally administered to Wistar rats for 10 days at different doses. On day 7, 8 mg/kg of cisplatin was administered intra-peritoneally to rats in all groups. T. chebula, in a dose-dependent manner significantly inhibited the elevation of serum creatinine, blood urea nitrogen and oxidant stress markers. The immunohistochemical analysis revealed the increased levels of apoptotic markers and cytokines in cisplatin group were significantly lowered by T. chebula extract. The cisplatin-treated rats kidney showed diffused tubular necrosis and infilteration of inflammatory cells which was reversed in the treatment group. Chemical characterisation of extract by HPLC revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and ellagic acid. The findings of this study discovered that T. chebula ameliorated oxidative and histological damage caused by cisplatin.

Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in wistar rats: by modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage

Doxorubicin (DXR) is one of the most important chemotherapeutic agent. However, nephrotoxicity reduces its clinical utility in humans. The aim of the study was to investigate protective effects of curcumin (CMN) against DXR-induced nephrotoxicity. Rats were subjected to oral treatment of CMN (100 and 200 mg/kg body weight) for 7 days. Nephrotoxicity was induced by single intra peritoneal injection of DXR (40 mg/kg body weight) on the fifth day and then the experiment was terminated on the eighth day. Nephroprotective effects of CMN were associated with decrease in serum toxicity markers and increase in antioxidant enzyme activities. CMN was able to reduced the levels of inflammatory markers such as TNF-α, NF-κB, IL-1β, iNOS and COX-2 in the rats. It also reduced the expressions of apoptotic marker including caspase-3, and oxidative DNA damage marker including 8-OHdG. Collectively, these findings indicated that CMN protect against DXR-induced nephrotoxicity.

Development of an Experimental Model of Nephrotoxicity Co-existing With Obesity in Rats

The present study attempted to develop an experimental model that would exhibit pathological features seen in individuals with obesity and nephrotoxicity suitable for pharmacological screening of drugs. A combination of high-fat diet and cisplatin at a dose of 5 mg/kg was used to induce obesity along with nephrotoxicity in Wistar rats. Animals were divided into four groups of six each. Group-I served as control, group-II served as obesity control, group-III served as nephrotoxicity control in normal rats to which cisplatin was injected on day 35 and group-IV rats served as nephrotoxic obese rats, which were fed with high fat diet and on day 35 nephrotoxicity was induced by a single cisplatin injection (5 mg/kg, ip). Various parameters that represent obesity and nephrotoxicity such as the body weight, lipid profile, blood glucose, liver function markers, serum creatinine, blood urea nitrogen, urinary total protein and creatinine clearance were estimated. The assessed parameters of obesity and nephrotoxicity indicated that in the group-IV animals and exhibited prominent nephrotoxicity compared to the group-III rats. Histological assessment of kidney and liver substantiated the findings from the biochemical parameters. In summary this study revealed that it is possible to develop a unique rodent model of nephrotoxicity co-existing with obesity.

Ameliorative potential of combination of Tribulus terrestris, Boerhaavia diffusa and Terminalia chebula against mercury chloride induced nephrotoxicity in Wistar rats

Ameliorative potential of combination of Tribulus terrestris, Boerhaavia diffusa and Terminalia chebula against mercury chloride induced nephrotoxicity in Wistar rats

The protective role of crocin in tartrazine induced nephrotoxicity in Wistar rats

The present study was conducted to investigate the changes in rat kidney tissues after administration of tartrazine (T) and crocine (Cr). The latter was applied for its protective properties. The present study was conducted with the approval of Inonu University, Faculty of Medicine, Experimental Animals Ethics Committee. Forty rats were randomly divided into 4 equal groups (Control, T, Cr, T + Cr). At the end of the experiment, the rats were decapitated. Biochemical and histopathological studies were conducted on excised rat kidney tissues. It was determined that there was a significant increase in MDA, TOS, SOD, CAT, Bun, Creatinine levels in tartrazine administered rat kidney tissues for 21 days, while GSH and TAS levels decreased (P ≤ 0.05) when compared to all other groups. On the other hand, it was identified that Cr administration statistically significantly increased GSH and TAS levels in rat kidney tissues when compared to all other groups and decreased MDA and TOS levels to control group levels (P < 0.05). T group kidney sections exhibited different degrees of collapse in the glomeruli. In most sections, different levels of inflammatory cell infiltration and vascular and capillary congestion were detected in peritubular interstitial tissue. It was determined that T leads to adverse effects on rat kidney tissues. Administration of Cr + T prevented T induced nephrotoxicity. Thus, it was concluded that Cr could be utilized as a new type of anti-tartrazine toxicity agent.

Protective potency of Meristotropis xanthioides against nephrotoxicity in a rat model along with its antioxidant and antibacterial activities.

To investigate nephroprotective potential of Meristotropis xanthioides (M.xanthioides) extract against ethanol-induced nephrotoxicity in Wistar rats, and also its total phenolics content, antioxidant and antibacterial activities. Total phenol and flavonoid amounts of the leaf and stem extracts were determined by Folin-Ciocalteu and aluminum chloride reagents, respectively. Antioxidant and antibacterial activities of the extracts were investigated by 2,2-diphenyl-1-picrylhydrazyl radical scavenging and disc diffusion methods, respectively. In addition, protective potential of the leaf extract against ethanol-induced nephrotoxicity was studied by histological and biochemical analyses. Obtained results indicated high total phenol [(10.26±0.46) mg GAE/g of dry extract] and flavonoid [(3.63±0.62) mg QE/g of dry extract] amounts in the leaf extract. The leaf and stem extracts possessed stronger antioxidant activity [IC50: (0.119±0.006) mg/mL and IC50: (0.133±0.009mg/mL)] than that of ascorbic acid [IC50: (0.142±0.002) mg/mL]. Also, the extracts showed good antibacterial activity against the most of bacteria taken in this research, especially Gram-positive ones. Histological examinations revealed tissue injury in the kidney of rats treated with ethanol. Results from biochemical assays showed reduction in total protein content and also in superoxide dismutase activity. In addition, remarkable increased levels (P<0.05) of H2O2 and malondialdehyde were found in ethanol-treated rats in comparison to control group. However, these injuries were significantly improved in rats treated by M.xanthioides leaf extract. Results from present study demonstrates strong pharmaceutical potential of M.xanthioides extract to apply as a new drug supplement.

Clinico-Biochemical and Nephroprotective Effects of Medicinal Herbs on Gentamicin Induced Nephrotoxicity in Wistar Rats

Nephrotoxicity followed by kidney disease is the main complication of gentamicin treatment. Medicinal plants and herbs have played an important role in the prevention and treatment of kidney diseases. With this concern the ethanol extract of Zingiber officinale rhizomes , ethanol extract of Tinospora cordifolia roots and methanol extract of Cajanus indicus leaves were compared for their nephroprotective effect in the Wistar rats. A total of 48 Wistar rats were distributed into six equal groups (n=8) and were exposed to gentamicin sulphate @ 100 mg/kg orally for 7 days to induce nephrotoxicity in 5 groups. Group G1 was kept as healthy control and group G2 was considered as untreated induced nephrotoxic control, whereas the rats of groups G3, G4, G5 and G6 were given, along with gentamicin sulphate @ 100 mg/kg, extracts of Zingiber officinale @ 400 mg/kg b.wt, Tinospora cordifolia 200 mg/kg b.wt, Cajanus indicus @ 400 mg/kg b.wt and syrup Cystone @ 500 mg/kg b.wt., respectively, orally for 7 consecutive days as neproprotective drugs. A significant (P less than 0.05) increase was observed in the values of plasma BUN, creatinine, urea, ALP, GGT, uric acid, calcium and phosphorus, whereas the total protein and albumin were found significantly (P less than 0.05) decreased on day 7 in rats receiving gentamicin alone (G2). However, there was no significant alteration in the values of above mentioned parameters in rats of G1 (healthy control), G4 and G6, which remained within the normal physiological range, suggesting nephroprotective role of herbal extracts in rats.

Protective effects of aqueous extract of cinnamon on diabetes-induced nephrotoxicity in wistar rats

Diabetes mellitus is a chronic metabolic disorder with multi-systemic adverse effects on the body. Cinnamon is atraditional folk herbsused for treatment of diseases and was popularas an embalming agent. The present study was undertaken to evaluate the effect of crude aqueous extract of Cinnamon for its protective activities on diabetes-induced nephrotoxicity in Wistarrats. Twenty-four adult Wistar rats of both sexes were assigned to three groups containing eight rats (n=8). Group A was the control group, group B was the streptozotocin-treated group, and group C was the streptozotocin followed by crude aqueous extract of Cinnamon treated group. Group B received 50mg/kg of STZ by the intraperitoneal (i.p.) injection. Group C received 50 mg/kg of STZ i.p. and 300 mg/kg/day of the aqueous extract of Cinnamon for 21 days. All the rats including the control group were fed with commercially formulated feeds and water ad`libidum for the same number of days. Effect of concurrent oral administration of crudeaqueous extract of Cinnamon at a dose of 300 mg/kg/day on the renal integrity was determined using serum creatinine, blood urea as indicators of kidney damage supporting histopathological findings. It was observed that the crude aqueous extract of Cinnamon significantly protect rat kidneys from diabetes-induced histopathological changes. This extract also normalized the increase in serumcreatinine and blood urea that characterized the diabetic group of rats.In conclusion, administration of aqueous extract of Cinnamon protects the kidneys of adult Wistar rats against diabetes-induced nephrotoxicity.Keywords: Aqueous extract, Cinnamon, Histological, Nephrotoxicity, Streptozotocin (STZ), Integrity

Gender differences in response to vitamin E and C in gentamicin induced nephrotoxicity in Wistar rats

Background: Nephrotoxicity is the most recognized side effect of gentamicin. Vitamin E and vitamin C demonstrate their effective role in the prevention of nephrotoxicity. Likewise, previous studies have suggested that women have low risk of end-stage renal disease at premenopausal period. to antioxidant effects vitamins E and C in gentamicin-induced nephrotoxicity. Materials and Methods: Wistar rats were randomly assigned to 6 groups each including both male and female rats. The first and second groups received saline (control group) and almond oil, the third group received gentamicin. The fourth group received a regular dose of gentamicin + vitamin E. Similarly, the fifth group received a regular dose of gentamicin + vitamin C. The sixth group received a dose of gentamicin + vitamin C and E simultaneously constantly. This protocol continued for 9 days. (MDA), but it decreased superoxidase dismutase (SOD) level (P < 0.05). Treatment with antioxidant vitamins improved urea, creatinine, MDA, and SOD serum level significantly in both genders (P <0.05). Likewise, kidney MDA level enhanced significantly (P <0.05) and treatment with antioxidant vitamins reduced MDA level too (P <0.05). Gentamicin decreased kidney SOD activity in male and female rats (P <0.05). However, treatment with antioxidant vitamins did not improve its level in male rats, while in female rats, vitamins E and C compensated for kidney SOD activity. genders, with some difference in response to vitamins E and C between the genders, that was higher in female rats.

English

This study was aimed to investigate the protective, ameliorative and preventive effects of aqueous Date fruit extract on paracetamol induced nephrotoxicity in wistar rats. A total of 30 male albino wistar rats were used for this study. Rats were randomly divided into five groups containing 6 animals each. Treatments were given daily for fourteen days. The animals in the control group (Group I) did not receive any treatment, while those in group 2 received paracetamol (2 g/kg/day). Group 3 were pretreated with aqueous date fruit extract (400 mg/kg/day) for a week before paracetamol administration. Rats in group 4 received paracetamol (2 g/kg/day) for a week before treatment with aqueous date palm extract (400 mg/kg). Group 5 was administered paracetamol (2 g/kg/day) in concurrent with 400 mg/kg aqueous date fruit extract. Exposure of rats with a nephrotoxic dose of paracetamol disturbed the kidney function tests; blood urea nitrogen (BUN) and serum creatinine (SC) levels increased significantly (P&gt;0.05). The protective use of aqueous date fruit extract on paracetamol-induced nephrotoxicity resulted in a significant improvement in most evaluated parameters. &nbsp; Key words: Date fruit, paracetamol, wistar rats, kidney.

295 - Chlorogenic Acid Represses 5-Fluorouracil Induced Renal Oxidative Stress, Apoptosis and Inflammation in Murine Model

5-Fluorouracil (5-FU) is a potent anti-neoplastic agent commonly used for the treatment of various malignancies. But it has varied detrimental effects such as nephrotoxicity, cardiotoxicity etc which limits its widespread clinical practice. Chlorogenic acid (CGA), esterified product of caffeic and quinic acids, is one of the most abundant polyphenol in human diet found in fruits and coffee drinks, possessing an array of biological properties like anti-oxidant, anti-inflammatory and anti-carcinogenic. In the present study, we investigated protective effect of CGA against 5-FU induced nephrotoxicity in wistar rats. The possible mechanism of nephrotoxicity may be ROS induced apoptosis and inflammation via up-regulating ROS generation, P53, bax, caspase-3, TNF-α, cox-2, iNOS, and down regulating Bcl-2. CGA was administered to Wistar rats daily for 20 consecutive days at 60 and 120 mg/kg body weight orally and on day 19, a single intra-peritoneal injection of 150 mg/kg body weight 5-FU was given. CGA ameliorated 5-FU induced LPO, increase in serum toxicity markers and replenished deficit in antioxidant armory. CGA also down regulated apoptotic and inflammatory tissue damage induced by 5-FU. Histological findings further supported biochemical and immunohistochemical results. Therefore results of the present study suggest that CGA may be used in combinational therapy to improve therapeutic index of 5-FU after further preclinical and clinical testing.