Experimental analgesic nephropathy: changes in renal structure and urinary concentrating ability in Fischer 344 rats given continuous low doses of aspirin and paracetamol

Long-term treatment with aspirin and paracetamol produced renal papillary necrosis in female Fischer 344 rats. Aspirin (230 mg/kg body weight/day) and paracetamol (380 mg/kg body weight/day) were dissolved in drinking water and given continuously for up to 65 weeks. Renal morphological changes were examined between 21 weeks and 65 weeks of commencement of analgesic treatment using light and electron microscopy, and were compared with age-matched controls. Structural damage initially occurred in the mid-papillary region, and specifically involved the interstitial cells and interstitial matrix. Necrosis of the epithelium of the thin limbs of the loop of Henle was present only after interstitial changes were well established. Cortical interstitial fibrosis and tubular atrophy occurred after renal papillary changes were observed. There was no evidence of significant vascular damage. Urinary concentrating ability was measured sequentially during the period of analgesic treatment. A decrease in urine concentrating ability was present when early changes to the interstitial cells and matrix were observed, and concentrating ability continued to decrease in parallel with increasing morphological damage. This study describes an animal model of analgesic-induced nephropathy, enabling early morphological changes to be studied and correlated with renal functional changes.     

Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats

Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.     

Spinal cholinergic involvement after treatment with aspirin and paracetamol in rats

Aspirin and paracetamol have been shown to suppress non-inflammatory pain conditions like thermal, visceral and mechanical pain in mice and rats. The non-inflammatory antinociception appears to be mediated by central receptor mechanisms, such as the cholinergic system. In this study, we tested the hypothesis that the non-inflammatory antinociception of aspirin and paracetamol could be mediated by an increase of intraspinal acetylcholine release. Microdialysis probes were placed intraspinally in anesthetized rats for acetylcholine sampling. Subcutaneously administered aspirin 100 and 300 mg/kg increased, while paracetamol 300 mg/kg decreased intraspinal acetylcholine release. Intraspinal drug administration did not affect acetylcholine release. Our results suggest that an increased intraspinal acetylcholine release could be involved in part of the non-inflammatory pain suppression by aspirin, but not by paracetamol.     

Effect of aging on urinary concentrating mechanism and vasopressin-dependent cAMP in rats

The effect of aging on urinary concentrating ability and the pathogenic mechanism involved were investigated in Fischer 344 rats. While the rats had free access to drinking water, 24-mo-old rats were polydipsic and polyuric compared with 6- and 12-mo-old rats. The maximum urinary concentrating ability after 40-58 h of water deprivation was not different between 6- and 12-mo-old rats (Uosmol 2,941 +/- 173 vs. 2,706 +/- 96 (SE) mosmol/kg), but it was significantly decreased in 24-mo-old rats (1,885 +/- 172 mosmol/kg, P less than 0.01). Similarly, although 5 mU/ml vasopressin increased the concentration of cAMP and papillary slices in 12-mo-old rats (delta +2.81 +/- 0.62 pmol/mg tissue, P less than 0.01), the same concentration of vasopressin failed to increase the cAMP concentration in 24-mo-old rats (delta +0.25 +/- 0.21 pmol/mg tissue, P greater than 0.05). In the adenylate cyclase preparation of renal papilla, the response to low concentrations of vasopressin was diminished in 24-mo-old rats. The dose-response curve was shifted to the right and the ED50 concentration of vasopressin was increased in 24-mo-old rats compared with 12-mo-old rats: 1.40 +/- 0.12 mU/ml vasopressin vs. 3.04 +/- 0.22. These results suggest that the decrease in vasopressin-dependent cAMP generation may in part be responsible for the impairment of urinary concentrating ability in 24-mo-old rats.     

Hepatoprotective effect of ethanolic extract of Trichosanthes lobata on paracetamol-induced liver toxicity in rats

ABSTRACT: BACKGROUND: Trichosanthes lobata (family cucurbitaceae) is used to treat malarial fever and liver disorders. This study aims to investigate possible hepatoprotective activities of ethanolic extract of Trichosanthes lobata against paracetamol-induced hepatotoxicity. METHODS: Hepatotoxicity was induced in Wistar male rats by oral administration, 2 g/kg body weight on 7th day after the administration of ethanolic extract of Trichosanthes lobata and silymarin (100 mg/kg). Ethanolic extract of Trichosanthes lobata was administered orally at doses of 200 mg/kg and 400 mg/kg body weight daily for 7 days. Several serum markers, aspartate transaminase, alanine transaminase, alkaline phosphatase, bilirubin, total protein was measured to assess the effect of the extract on paracetamol (acetaminophen)-induced hepatic damage. The study included histopathological examination of liver sections. RESULTS: Blood samples from rats treated with ethanolic extract of Trichosanthes lobata (200 mg/kg body weight and 400 mg/kg body weight) had significant reductions in serum markers in paracetamol administered animals, indicating the effect of the extract in restoring the normal functional ability of hepatocytes. Silymarin (100 mg/kg, p.o.) was used as a reference drug. CONCLUSION: The ethanolic extract of Trichosanthes lobata exhibits protective effects against paracetamolinduced hepatotoxicity.     

Electron microscopic observations comparing the gastric mucosal damage induced in rats and pigs by benoxaprofen and aspirin,reflecting their differing actions as prostaglandin-synthesis-inhibitors.

The ultrastructural changes in the gastric mucosa induced by oral administration of aspirin (2 x 125 mg/kg/day) were compared with the effects of benoxaprofen (20 mg/kg/day) in pigs and normal and arthritic rats after 10 or 14 days'' treatment respectively. The object was to compare the effects of drugs having different effects on prostaglandin-synthesizing systems on the development of gastric mucosal damage. Benoxaprofen caused less gastric damage than aspirin. There were fewer lesions in benoxaprofen-treated animals and those which were seen were much less extensive. There were qualitative similarities between the effects of the drug treatments. There were also differences in the mucosal changes produced by both drugs in pigs and rats. This included (1) extravasation of erythrocytes which was seen in rats but not pigs, and (2) interstitial changes also seen in rats but not pigs. These interspecies variations may be due to differences in the resistance of the capillaries to drug effects. There were no differences in the mucosal-cell damage seen in normal compared with arthritic rats.     

Renoprotective effect of a dopamine D3 receptor antagonist in experimental type II diabetes

Diabetic nephropathy is the leading cause of end-stage renal disease. Dopamine receptors are involved in the regulation of renal hemodynamics and may play a role in diabetes-induced hyperfiltration. To test this hypothesis, we investigated the renal effect of a dopamine D3 receptor antagonist (D3-RA) in hypertensive type II diabetic SHR/N-cp rats. Lean and obese SHR/N-cp rats were randomly assigned to D3-RA, angiotensin-converting enzyme inhibitor (ACE-i), or D3-RA+ACE-i treatment or control conditions. Treated animals were given the D3-RA A-437203 (10 mg/kg/body weight (BW)/day) or the ACE-i trandolapril (0.3 mg/kg BW/day) or a combination of both. At 6 months following perfusion, fixed kidneys were analyzed by morphological and stereological methods. Indices of renal damage (glomerulosclerosis, glomerulosclerosis damage index (GSI), tubulointerstitial and vascular damage), glomerular geometry and functional variables such as urinary albumin excretion, glomerular filtration rate, blood pressure, blood chemistry and BW were determined. The GSI (score 0-4) was significantly higher (P<0.05) in untreated diabetic animals (1.62+/-0.3) compared to nondiabetic controls (0.4+/-0.2) and the treatment groups (D3-RA: 0.31+/-0.12; ACE-i: 0.29+/-0.1; combination treatment: 0.12+/-0.01). Urinary albumin excretion (mg/24 h) was higher in untreated diabetic controls (102+/-19) compared to nondiabetic controls (31+/-12) and the treatment groups (D3-RA: 44+/-15; ACE-i: 41+/-13; combination treatment: 15+/-8). Mean glomerular volume was higher in untreated diabetic animals compared to nondiabetic controls and to the treatment groups. Desmin expression, a marker of podocyte damage, was elevated in untreated diabetic controls and diminished in all treatment groups. These data suggest that in a model of type II diabetes, the dopamine D3-RA had a beneficial effect on renal morphology and albuminuria, which was comparable in magnitude to that of ACE-i treatment.     

Effects of a therapy with losartan and quinaprilat on the progression of chronic renal failure in rats after a single dose of uranyl nitrate or 5/6 nephrectomy

The renoprotective effect of losartan and quinaprilat was tested in two different animal models of renal failure [female Wistar rats, single administration of 0.5 mg uranyl nitrate (UN)/100 g body wt. or 5/6 nephrectomy (5/6NX)]. Losartan (1 mg/100 g body weight [wt.]) and quinaprilat (1mg/100 g body wt.) were administered intraperitoneally, once daily, starting 10 days after UN and one week after 5/6NX till the end of 10 weeks experimental period. Parameters characterizing the therapeutic effect were blood pressure, urinary protein excretion 4 and 10 weeks after the injury, and p-aminohippurate accumulation in renal cortical slices in vitro, hydroxy-proline concentration in renal tissue and morphology at the end of the experiment.

Summarizing our results we state: (1) the angiotensin 1 receptor blocker losartan is more effective in UN-treated than in 5/6 NX rats, and (2) the angiotensin converting enzyme inhibitor quinaprilat is more effective than losartan because of the amelioration of blood pressure and OH-proline concentration in renal tissue of UN-treated rats.     

Mechanisms of impaired urinary concentrating ability in adult rats treated neonatally with enalapril

Neonatal angiotensin-converting enzyme inhibition or angiotensin II type-1 receptor blockade induces irreversible renal histological abnormalities and an impaired urinary concentrating ability in the rat. The aim of the present study was to determine the pathophysiological mechanisms underlying the defect in urine concentration in adult rats treated neonatally with enalapril. Male Wistar rats received daily intraperitoneal injections of enalapril (10 mg kg(-1)) or saline vehicle from 3 to 24 days of age. Assessments of fluid handling and maximal urine osmolality (Uosm(max)), renal function and tubular free water reabsorption (T(c)H2O) under pentobarbital anaesthesia, renal tissue solute concentrations, renal aquaporin-2 (AQP2) expression, and kidney histology, were performed in 12-16-week-old rats. Uosm(max) (1488 +/- 109 vs. 2858 +/- 116 mosm kg(-1), P < 0.05) and maximal T(c)H2O were reduced in enalapril- vs. vehicle-treated rats after administration of 1-desamino-8-D-arginine vasopressin. Neonatally enalapril-treated rats showed marked papillary atrophy, a decrease in medullary tissue solute concentrations, and a reduction in AQP2 expression specifically in the inner medulla. Glomerular filtration rate, renal plasma flow and urinary excretion rates of sodium, potassium and chloride did not differ between groups. In conclusion, adult rats treated neonatally with enalapril showed a urinary concentrating defect of renal origin which primarily could be explained by the papillary atrophy. However, an impaired ability to generate medullary interstitial hypertonicity, and a decrease in inner medullary AQP2 expression, also seem to contribute to this defect.     

Tubular response to hormones is blunted in weanling rats

The renal responses to atrial natriuretic peptide (ANP), parathyroid hormone (PTH) and arginine vasopressin (AVP) were studied in anaesthetized weanling and adult rats with clearance methods. In rats receiving PTH, thyroparathyroidectomy (TPTX) was performed prior to the study. The results showed that GRF remained unchanged in both age groups during infusion with ANP, AVP and PTH after TPTX as well as with TPTX alone. During ANP infusion, the urine flow rate increased from 0.01 +/- 0.002 to 0.029 +/- 0.004 ml (100 g body wt)-1 min-1 (P less than 0.001) and the fractional sodium excretion increased from 0.48 +/- 0.1 to 3.0 +/- 0.4% (P less than 0.001) in the adult rats; no significant changes were observed in the weanling rats. Phosphate excretion was not influenced by ANP in either age group. After TPTX, both net and fractional phosphate excretion decreased in both age groups. During PTH infusion in TPTX rats, both net and fractional phosphate excretions increased significantly in the adult rats but were unchanged in the weanling rats. In rats of the same age, the renal concentrating capacity and urinary excretion of prostaglandin E2 (PGE2) were determined after dehydration. The renal concentrating capacity was lower, and the renal excretion of PGE2 was higher, in the weanling than in the adult rats. Furthermore, the concentrating mechanism seems not to be influenced by indomethacin treatment in either age group. It is concluded that the tubular responses to ANP and PTH are blunted in the immature kidney and that the renal excretion of PGE2 is not an important factor in the regulation of the concentrating capacity in the weanling rat.     

The protective effects of aqueous extract of Carica papaya seeds in paracetamol induced nephrotoxicity in male wistar rats

Background

Oxidative stress plays a crucial role in the development of drug induced nephrotoxicity. The study aimed to determine the nephroprotective and ameliorative effects of Carica papaya seed extract in paracetamol-induced nephrotoxicity in rats.

Objectives

To carry out phytochemical screening of Carica papaya, measure serum urea, creatinine and uric acid and describe the histopathological status of the kidneys in the treated and untreated groups.

Methods

Phytochemical screening of the extract was done. Thirty two adult male Wistar rats were divided into four groups (n= 8 in each group). Group A (control) animals received normal saline for seven days, group B (paracetamol group) received normal saline, and paracetamol single dose on the 8th day. Group C received Carica papaya extract (CPE) 500 mg/kg, and paracetamol on the 8th day, while group D, rats were pretreated with CPE 750 mg/kg/day,and paracetamol administration on the 8th day. Samples of kidney tissue were removed for histopathological examination.

Results

Screening of Carica papaya showed presence of nephroprotective pytochemicals. Paracetamol administration resulted in significant elevation of renal function markers. CPE ameliorated the effect of paracetamol by reducing the markers as well as reversing the paracetamol-induced changes in kidney architecture.

Conclusion

Carica papaya contains nephroprotective phytochemicals and may be useful in preventing kidney damage induced by paracetamol.     

Concentration and dilution of the urine in partially hepatectomized,conscious rats

1. The influence of partial hepatectomy on urinary concentrating ability and renal tissue sodium was determined in conscious rats deprived of water for 24 h. In comparison with a sham operation, partial hepatectomy resulted in: a) a 50% reduction in free-water reabsorption, urinary osmolality, and osmolal urine-to-plasma ratio; b) depression of free-water reabsorption at similar levels of osmolal clearance above 200 microliter/min per ml of GFR during the infusion of hypertonic NaCl and vasopressin; and c) a 30% reduction in sodium content of the renal papilla and outer medulla. 2. The renal response to an intravenous water load (2.5% glucose infused to 2.5% of body wt at 0.4 ml/min) was determined in sham-operated and partially hepatectomized, conscious rats. By 60 min after the water load, both groups had excreted practically all of the load. However, during and for 30 min after the infusion in the partially hepatectomized group, the percent of the water load excreted, urine flow, and free-water clearance were significantly reduced while urinary osmolality and osmolal urine-to-plasma ratio were significantly elevated. 3. These experiments demonstrate that shortly after partial removal of the liver the renal concentrating ability is defective and the excretion of a water load is not grossly impaired.     

Gentamicin-induced nephrotoxicity in mice: protection by loop diuretics.

Gentamicin, at doses of 50 or 100 mg/kg body wt administered daily to healthy male MF1 mice by i.p. injection for either 7 or 10 days caused proximal tubular cell damage shown both by the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and by electron microscopy. The tubular damage was maximal at 7 days. Concomitant administration of any of 3 diuretics-frusemide, bumetanide or piretanide at 5,0.5 and 1 mg/kg body wt/day respectively-resulted in less tubular damage than that caused by gentamicin alone. This finding of protection by diuretics contrasts with those of previous studies of combination gentamicin-diuretic therapy.     

Protective effects of Chlorpromazine and Verapamil against cadmium-induced kidney damage in vivo

Overexposure to cadmium (Cd) can induce kidney damage, which was related to the oxidative damage and disturb intracellular Ca²⁺ homeostasis. Chlorpromazine (CPZ), targeting calmodulin (CaM), and the Ca²⁺ channel blocker Verapamil (Ver) are involved in intracellular Ca²⁺ homeostasis processes. The aim of the study was to investigate the kidney damage caused by Cd administrated for 6 weeks and to evaluate the effects of pre-treatment with either chlorpromazine or verapamil on Cd-induced kidney damage. Thirty-two Wistar rats were divided randomly into 4 groups by weight, i.e., control group, Cd-treated group, and CPZ or Ver pre-treated group. The Cd-treated group rats were subcutaneously (s.c.) injected with 7 μmol CdCl₂/kg body weight/day. The CPZ and Ver pre-treated group rats were intraperitoneally (i.p.) injected with 5 mg CPZ/kg body weight/day, 4 mg Ver/kg body weight/day, respectively, 1 h before the s.c. administration of 7 μmol CdCl₂/kg body weight/day. The control group rats were injected s.c. with saline at the same time. The volume of injection was 2 ml/kg body weight, 5 times per week, for up to 6 weeks. After 6 weeks, Cd concentrations in the renal cortex and urine were significantly higher in Cd-treated group than that in controls. Cd concentrations of the urine in CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated group, but there were no significant changes in the renal cortex. Compared with the controls, urinary NAG, ALP activities, and the levels of GSH, MDA, and the activities of PKC, Na⁺–K⁺-ATPase, and Ca²⁺-ATPase in rats from the Cd-treated group were significantly increased. SOD activity was suppressed by Cd. Urinary NAG activity and the level of GSH and the activities of PKC and Ca²⁺-ATPase in both CPZ and Ver pre-treated groups were significantly lower than that in Cd-treated rats. The present results showed that Cd-induced kidney damage was related to the oxidative damage and disturb intracellular Ca²⁺ homeostasis. Both CPZ and Ver possess some ability to prevent cadmium-induced kidney damage via antioxidative action and by maintaining calcium homeostasis.     

Renin-angiotensin system in stroke-prone spontaneously hypertensive rats.

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.     

The duration of the pulmonary paraquat toxicity--enhancement effect of O2 in the rat

The duration of the pulmonary paraquat toxicity-enhancement effect of O2 has been examined in Wistar rats. In one experiment, various groups of normal animals were given a single dose (5 mg/kg body wt) of paraquat and after different periods were exposed to continuous breathing of normobaric 74% O2 in airtight chambers until dead or up to 10 days. In a reverse experiment, a large number of rats were first exposed for 6 days to continuous breathing of normobaric 74% O2 and were then separated into various groups which received a single dose of paraquat (5 mg/kg body wt) after various periods of breathing normal air, ranging from 0 to 96 hr. The extent of pulmonary damage in both experiments was evaluated by histologic examination and by biochemical determination of total collagen content of the lungs. It was found that the duration of the pulmonary damage induced by paraquat that is enhanced by continuous breathing of high O2 concentration lasts 24 to 48 hr. It was also observed that 12 to 24 hr after paraquat administration and continuous breathing of high O2 concentration pulmonary lesions are severe and extensive, and in animals surviving 6 or more days there was also incipient interstitial fibrosis. The reverse sequence of treatment (O2 + paraquat) resulted in no mortality and no pulmonary lesions. Additional controls treated with each of the pulmonary toxins alone also revealed no lung changes.     

全反式维甲酸对生长发育期大鼠实质器官的损伤

目的 探讨体内过量全反式维甲酸（ATRA）对生长发育期SD大鼠的脑、心、肺、肝、肾和脾的影响。方法 以48只3周雄性SD大鼠为实验对象,随机分为对照组和3个实验组,ATRA剂量分别为40、60、80 mg/(kg·d),每组12只,进行连续10 d ATRA灌胃处理,记录SD大鼠每日体重,于灌胃第10天解剖称量各器官的重量以及计算脏器指数,然后对各器官进行HE染色。结果 ATRA灌胃后,与对照组比较,40 mg/(kg·d) ATRA组肾指数升高,体重变化差异无统计学意义;60 mg/(kg·d) ATRA组体重降低,心、肾指数升高,脾脏重量降低;80 mg/(kg·d)ATRA组体重明显降低,脑、心、肾指数升高,脑、脾重量降低;HE染色显示,与对照组比较,ATRA处理组的肺泡壁增厚,肾小管上皮细胞有空泡样改变,脾脏红髓出现较多巨噬细胞,而大脑、肝脏、心肌无明显组织学变化。结论 体内过量全反式维甲酸能够对生长发育期SD大鼠的肺、肾和脾有一定的损伤作用。     

Effect of aspirin on the expression of hepatocyte NF-κB and serum TNF-α in streptozotocin-induced type 2 diabetic rats

Aspirin is a kind of anti-inflammatory drug and may be used to reverse hyperglycemia, hyperinsulinemia, and dyslipidemia by improving insulin resistance. We hypothesized that aspirin improves insulin resistance in type 2 diabetes by inhibiting hepatic nuclear factor kappa-β (NF-κB) activation and serum tumor necrosis factor-α (TNF-α). Adult male Wistar rats were randomly divided into four groups: control, untreated diabetic, diabetic treated with metformin (100 mg/kg/day), and diabetic treated with aspirin (120 mg/kg/day). Diabetes was induced by high-fat feeding and a low dose of streptozotocin (30 mg/kg). After treatment, plasma glucose, insulin, lipids, free fatty acids (FFAs) concentrations and serum TNF-α were determined. The expression of NF-κB in hepatocytes was analyzed by immunohistochemistry and western blot. The results showed administration of aspirin caused no significant lowering in fasting glucose level but significant reduction of hepatic NF-κB expression and serum TNF-α level with improved insulin resistance compared to the diabetic group. The relevant analysis showed positive correlation between the expression of homeostasis model assessment-insulin resistance (HOMA-IR) and NF-κB (r = 0.799, P < 0.01); HOMA-IR and serum TNF-α (r = 0.790, P < 0.01). It is concluded that aspirin improves insulin resistance by inhibiting hepatic NF-κB activation and TNF-α level in streptozotocin-induced type 2 diabetic rats.     

Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion.

Gentamicin sulphate was administered to male Wistar rats by intramuscular injection at varying dosage and for varying periods. At high dosage (50-100 mg/kg/day) gentamicin causes tubular necrosis. At dosages equivalent to that given to man (5 mg/kg/day) obvious degenerative changes are produced. Similar changes are seen in human tubular epithelium and urine deposits of patients treated with gentamicin. There is increased excretion of urinary enzymes proportional to the degree of tubular damage. The importance of these changes in man is stressed.     

Efficacy of Raphanus sativus in the treatment of paracetamol-induced hepatotoxicity in albino rats

In the present study, the efficacy of a methanol extract of Raphanus sativus root (RSME) is tested in albino rats that developed hepatic damage due to administration of paracetamol (100 mg/kg body weight) for 30 days. Twenty rats were divided into three experimental groups (E1, E2, E3) and one control group (EC). Two doses of RSME (80 and 120 mg/kg body weight) were administered orally to E1 and E2, respectively, and a mixture of RSME (120 mg/kg) and paracetamol (100 mg/kg) was administered to E3 for 21 days. Group EC and another group of normal rats (EN) that served as controls were administered distilled water. At the end of the experiment rats were bled to assay thiobarbituric acid reactive substances (TBARS), serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate aspartate transaminase (SGPT), reduced glutathione (GSH) and catalase. Results indicated that RSME reduced the levels of TBARS, SGOT and SGPT, and increased the level of GSH and the catalase activity in E1 and E2 as compared to the EC group. Group E3 showed decreases in TBARS, SGOT and SGPT levels, but the results were not statistically significant compared with the EN group. There was also a marked depletion in GSH level and catalase activity in this group. RSME reduced lipid peroxidation induced by paracetamol and brought the levels of SGOT and SGPT to normal, indicating liver recovery. It also brought about repletion of GSH levels and recovery of catalase activity. Results for group E3 indicated that RSME was not able to reverse the effects of paracetamol if administration continued.