Attenuation of oxidative stress by syringic acid on acetaminophen-induced nephrotoxic rats

This study was aimed to evaluate the preventive efficacy of syringic acid (SA) on acetaminophen (APAP)-induced nephrotoxicity. Nephrotoxicity was induced in male Wistar albino rats by the administration of a single dose of 750?mg/kg APAP intraperitoneally. In this study, we evaluated the levels of renal markers, lipid peroxidation markers (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH)), enzymatic and nonenzymatic antioxidant status, and histopathological changes of kidney. Our results show significant (P?<?0.05) increased levels of serum urea, uric acid, creatinine, and TBARS, LOOH in the kidney tissue. In addition, the activities of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione levels significantly (P?<?0.05) decreased in the kidney of APAP nephrotoxic rats. Moreover, histopathological observations also correlated with the biochemical findings to improved morphological changes including tubular epithelial degeneration, vacuolization, cell desquamation, and necrosis. Oral administration of SA (50?mg/kg body weight) to APAP rats for 6?days prevented the above biochemical and renal morphology changes and improved towards normalcy. These findings suggested that the protective effects of SA against APAP-induced kidney injuries might result from the amelioration of APAP-induced oxidative stress.     

Effect of quercetin against dichlorvos induced nephrotoxicity in rats

This study was carried out to determine the effect of quercetin against renal injury induced by dichlorvos (DDVP) in rats. Rats were randomly assigned to control, DDVP-treated (7.2 mg/kg bw), three different doses of quercetin-treated (2 mg/kg bw, 10 mg/kg bw, 50 mg/kg bw) and different doses of quercetin plus DDVP-treated groups. DDVP was administered daily to rats through their drinking water, and quercetin was administered by intragastric gavage for 90 days. By the end of the 90th day in the DDVP-treated group, the following indices significantly increased compared with the control (P < 0.01): activities of catalase, glutathione peroxidase and superoxide dismutase; level of malondialdehyde in kidney tissues; serum levels of creatinine and urea nitrogen; and level of β2-microglobulin, level of retinol-conjugated protein, and activity of N-acetyl-β-d-glucosaminidase in urine; by contrast, urine uric acid levels significantly decreased. However, in the quercetin (50 mg/kg bw) plus DDVP group, the aforementioned indices were significantly decreased compared with the DDVP-treated group (P < 0.05), except the urine uric acid levels were significantly increased (P < 0.05). Thus, rat exposure to DDVP caused renal injury, including renal tubular, glomerular filtration, and oxidative stress. These toxic effects were also regulated by high-dose quercetin. Histopathological examination revealed that exposure to DDVP induced extensive cell vacuolar denaturation, but milder histopathological alterations in the kidney tissues of rats co-treated with DDVP and quercetin (50 mg/kg bw) were observed. These results indicated that quercetin at 50 mg/kg bw can partly prevent the kidney injury induced by DDVP.     

Prevention of cisplatin induced nephrotoxicity by terpenes isolated from Ganoderma lucidum occurring in Southern Parts of India

Investigations were carried out to determine the protective effect of terpenes isolated from the fruiting bodies of Ganoderma lucidum (Fr) P.Karst against nephrotoxicity caused by the cisplatin, in mice. Intraperitoneal administration of cisplatin (16 mg/kg body wt) resulted in significant nephrotoxicity in mice. Serum urea, creatinine and ALP levels were drastically elevated indicating severe nephrotoxicity . The renal antioxidant defense system such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and concentration of reduced glutathione (GSH) were depleted by cisplatin injection. The oral administration of terpenes at a dose of 100 mg/kg body weight prevented increase in urea, creatinine levels and ALP activity and also maintained the renal antioxidant defense. The Ganoderma terpenes also imparted protection against cisplatin induced renal tissue lipid peroxidation. The results indicated that the total terpenes isolated from G. lucidum possessed significant in vivo antioxidant activity and rendered protection against cisplatin induced nephrotoxicity. The results suggest the potential therapeutic use of Ganoderma terpenes to prevent nephrotoxicity caused during chemotherapy using cisplatin.     

Toxic effects of lambda-cyhalothrin,a synthetic pyrethroid pesticide,on the rat kidney: Involvement of oxidative stress and protective role of ascorbic acid

Lambda-cyhalothrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The objective of this study was to investigate the propensity of lambda-cyhalothrin (LTC) to induce oxidative stress, changes in biochemical parameters and enzyme activities in the kidney of male rats and its possible attenuation by Vitamin C (vit C). Renal function, histopathology, tissue malondialdehyde (MDA), protein carbonyl (PCO) levels, antioxidant enzyme activities and reduced glutathione (GSH) levels were evaluated. Exposure of rats to lambda-cyhalothrin, during 3 weeks, caused a significant increase in kidney MDA and protein carbonyl levels (p<0.01) as compared to controls. Co-administration of vitamin C was effective in reducing MDA and PCO levels. The kidney of LTC-treated rats exhibited severe vacuolations, cells infiltration and widened tubular lumen. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) were significantly decreased due to lambda-cyhalothrin exposure. Co-administration of vitamin C ameliorated the increase in enzymatic activities of aminotransferases (AST and ALT), lactate dehydrogenase (LDH), creatinine and urea levels and improved the antioxidant status.These data indicated the protective role of ascorbic acid against lambda-cyhalothrin-induced nephrotoxicity and suggested a significant contribution of its antioxidant property to these beneficial effects.     

Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats

The aim of this study was focused on investigating the possible protective effect of NS against GS-induced nephrotoxicity. Twenty four Wistar-albino rats were divided into four equal groups as follows: control group, GS group (100 mg/kg intraperitoneal – i.p.), NSL+GS group (0.2 ml/kg+100 mg/kg i.p.) and NSH+GS group (0.4 ml/kg+100 mg/kg i.p.). Plasma creatinine and urea levels significantly increased as a result of nephrotoxicity in the GS group. Also, creatinine and urea levels significantly decreased in NSL+GS and NSH+GS groups. In the GS group, plasma MDA and NO levels increased significantly (p<0.05) and erythrocyte SOD and GSH-Px activities decreased significantly (p<0.05) when compared with control group. NS administration with GS injection resulted in significantly decreased MDA and NO generation and increased SOD and GSH-Px activities when compared with GS group. Proximal tubular necrosis, vacuolation, desquamation and degeneration in epithelial cells of the proximal tubules, hyaline casts in tubular lumen, mononuclear cell infiltration, glomerular and basement membrane alterations were histopathologically detected in the kidneys of the GS group. Co-treatments with NS (low and high dose) considerably decreased the renal damage when compared with the GS group. In conclusion, NS acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GS both in the biochemical and histopathological parameters.     

Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress

Introduction

Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue. Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative properties. This study was performed to assess the effects of quercetin on lipopolysaccharide (LPS)-induced ALI.

Material and methods

Sprague-Dawley rats were randomly divided into 3 groups: the control group (saline alone), the LPS group challenged with LPS (Escherichia coli 026:B6; 100 µg/kg), and the quercetin group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge. Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h after LPS administration. Histopathological and biochemical parameters were measured.

Results

The LPS treatment led to increased alveolar wall thickening and cellular infiltration in the lung, which was markedly prevented by quercetin pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the increase in the BALF protein level and neutrophil count and lung wet/dry weight ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-α and interleukin-6, which was significantly (p < 0.05) counteracted by quercetin pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the malondialdehyde level and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the lung of LPS-treated rats.

Conclusions

Quercetin pretreatment effectively ameliorates LPS-induced ALI, largely through suppression of inflammation and oxidative stress, and may thus have therapeutic potential in the prevention of this disease.     

Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation.     

Nephrotoxic effect of tetradifon in rats: A biochemical and histomorphometric study

The effects of subchronic exposure to tetradifon on biochemical related kidney toxicological parameters [creatinine (CRT), urea, and uric acid (UA)] were examined. Oxidative stress in kidney tissue was also assessed by measuring vitamin C (VitC) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)]. Tetradifon was administered orally to 12 rats at a cumulative dose of 24.3 mg/kg for 12 weeks. Twelve additional rats, no treated, have served as control. Control and treated animals were sacrificed after 6 or 12 weeks. For each group, kidneys were examined for morphometric changes. Results showed that tetradifon induced significant increases in CRT and urea, and decrease in UA. Morphometrically, while mean glomerular volume decreased percentage of sclerosed glomeruli increased in treated rats. Index of interstitial fibrosis was significantly higher. Moreover, renal antioxidant enzyme (SOD and GPx) activities and VitC content decreased. We concluded that tetradifon possessed nephrotoxic by promoting kidney morphometric and functional damage and depleting renal antioxidant defense system in rats.     

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p < 0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.     

Protective effect of Phyllanthus niruri against cyclosporine A-induced nephrotoxicity in rats

Phyllanthus niruri (Euphorbiaceae) is a popular plant in folk medicine, whole plant, fresh leaves, and fruits are used in the treatment of various diseases. In the present study, nephroprotective potential of aqueous extract of P. niruri was investigated against cyclosporine A (CsA) induced changes in kidney of Wistar rats. Nephrotoxicity was induced by oral administration of CsA (25 mg/kg/b.w.) dissolved in olive oil for a period of 21 days. Nephrotoxicity induced rats were treated with aqueous extract of P. niruri (200 mg/kg/b.w.) for a period of 21 days. Levels of serum creatinine and blood urea nitrogen, renal marker enzymes in serum and different enzymic and non-enzymic antioxidants, lipid peroxidation products, as well as ATPases in kidney homogenates were measured in normal, control (toxicity induced), and P. niruri treated rats. Histopathological studies were also been carried out. Administration of CsA increased the serum levels of creatinine and blood urea nitrogen, alkaline phosphatase, alanine aminotransaminase, and lactate dehydrogenase thereby indicating damage to kidneys. Increased lipid peroxidation and a decrease in antioxidants enzymes were observed in toxicity-induced rats. The levels of membrane-bound ATPases were also significantly altered. Upon administration of P. niruri, the levels of serum creatinine and blood urea nitrogen and also lipid peroxidation were found to be markedly reduced. Renal antioxidant defense systems, such as superoxide dismutase, catalase, glutathione peroxidase activities and reduced glutathione, and vitamins e and c, depleted by cyclosporine A, were restored to normalcy by treatment with the extract. The drug also effectively attenuated renal dysfunction and normalized the altered renal morphology and also restored the activities of renal ATPases. The results suggest that the nephroprotective effect of P. niruri could be due to the inherent antioxidant and free-radical scavenging principle(s) contained in the extract. In conclusion, our study indicates that P. niruri through its antioxidant activity effectively salvaged CsA induced nephrotoxicity.     

Urinary procollagen III aminoterminal propeptide and β-catenin – New diagnostic biomarkers in solitary functioning kidney?

Purpose: We aimed at evaluating urinary levels of procollagen III aminoterminal propeptide (PIIINP) and β-catenin and the relationship between these markers and clinical and laboratory variables in children with a solitary functioning kidney (SFK).Patients and methods: The study group consisted of 98 (M/F: 62/36) children with an SFK with a median age of 8 years. An age-matched control group contained 54 healthy peers. Urinary levels of procollagen III aminoterminal propeptide and β-catenin were measured using a commercially available immunoassay kit.Results: The urinary values of PIIINP (UPIIINP) were significantly increased in patients with SFK versus controls (p < 0.01). Our analysis revealed no significant differences in urinary β-catenin levels between the SFK patients and control subjects (p > 0.05). Only urinary PIIINP levels were correlated to renal function tests, such as serum creatinine, urea, uric acid, and estimated glomerular filtration rate (p<0.05).Conclusions: An increased urinary level of PIIINP may indicate early kidney impairment in children with SFK. Urinary β-catenin does not seem to play any important role as a marker of renal function in children with SFK. Further long-term studies are required in order to evaluate the clinical usefulness of these markers and their predictive value of chronic kidney disease (CKD) progression.     

Aqueous extract of Terminalia arjuna prevents cyclosporine-induced renal disorders

Cyclosporine (CsA), a powerful immunosuppressant, had a significant impact on transplantation medicine, and exposure to this chemical is known to induce oxidative stress and causes renal injury by the formation of free radicals. Acute and chronic renal damage are very common pathophysiologic disturbances caused by CsA. The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Terminalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CsA-induced oxidative stress and resultant dysfunction in the rat kidney. Animals were treated with the aqueous extract of TA (100 mg/kg body weight (b.wt)) and then treated with CsA (25 mg/kg b.wt) in olive oil for 14 days. The level of urea, uric acid, and creatinine was determined from serum sample. The enzymes, namely, alkaline phosphatase (ALP), acid phosphatase (ACP), aspartate transaminase (AST), and alanine transaminase (ALT), and enzymic indices of membrane integrity such as Na⁺K⁺ATPase, Ca²⁺ATPase, and Mg²⁺ATPases were estimated in the tissue of all study groups. Antioxidant status in kidney tissues was estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione transferase (GST) and the levels of reduced glutathione, vitamin E, and vitamin C. In addition, the kidney phospholipids, cholesterol, triglycerides, and free fatty acids were determined in the tissue. Results showed that CsA caused a marked increase in the levels of urea, uric acid, and creatinine in serum and decreases the levels of ALP, ACP, AST, ALT, Na⁺K⁺ATPase, Ca²⁺ATPase, Mg²⁺ATPases, SOD, CAT, glutathione reductase, GST, GPx, vitamin E, and vitamin C whereas cholesterol, triglycerides, free fatty acid, and phospholipid levels were found to be increased in the kidney tissue homogenates of CsA-treated rats. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. Our study demonstrated that the aqueous extract of the bark of TA could protect the kidney tissues against CsA-induced oxidative stress probably by increasing antioxidative defense activities.     

Quercetin protects jejunal mucosa from experimental intestinal ischemia reperfusion injury by activation of CD68 positive cells

The aim of our study was to analyse the possible protective effect of quercetin application during the jejunal ischemia-reperfusion injury (IRI) in rats. Quercetin was administered intraperitoneally 30 min before 1 h ischemia of superior mesenteric artery with following 24 h lasting reperfusion period. The male specific pathogen-free (SPF) Charles River Wistar rats were used. In the group with applied quercetin, the significantly increased (p < 0.001) levels of anti-inflammatory cytokine IL10 were observed both in the blood serum and jejunal tissue. The improvement of the mucosal tissue morphology and proliferating and DNA repairing cell number measured by PCNA activity were recorded by more than 30% higher in the quercetin group. Simultaneously, significant elongation of the intestinal glands (p < 0.001) and increase in the number of CD68-positive cells in the lamina propria mucosae (p < 0.001) in comparison with control group were found. Based on our results, the preventive application of quercetin before induction of jejunal IRI stimulates faster jejunal mucosa restoration and it seems to have immunomodulatory and anti-inflammatory effects as well. CD68-positive macrophages could have crucial role in this process since they work as both growth factor and cytokine producers.     

Role of quercetin and arginine in ameliorating nano zinc oxide-induced nephrotoxicity in rats

Background

Nanoparticles are small-scale substances (<100?nm) with unique properties. Therefore, nanoparticles pose complex health risk implications. The objective of this study was to detect whether treatment with quercetin (Qur) and/or arginine (Arg) ameliorated nephrotoxicity induced by two different doses of nano zinc oxide (n-ZnO) particles.

Method

ZnO nanoparticles were administered orally in two doses (either 600?mg or 1?g/Kg body weight/day for 5 conscutive days) to Wister albino rats. In order to detect the protective effects of the studied antioxidants against n-ZnO induced nepherotoxicity, different biochemical parameters were investigated. Moreover, histopathological examination of kidney tissue was performed.

Results

Nano zinc oxide-induced nephrotoxicity was confirmed by the elevation in serum inflammatory markers including: tumor necrosis factor alpha (TNF-??), interleukin-6 (IL-6); and C-reactive protein (CRP). Moreover, immunoglobulin (IGg), vascular endothelium growth factor (VEGF), and nitric oxide (NO) were significantly increased in rat serum. Serum urea and creatinine levels were also significantly increased in rats intoxicated with n-ZnO particles compared with the control group. Additionally, a significant decrease in the non-enzymatic antioxidant reduced glutathione (GSH) was shown in kidney tissues and serum glucose levels were increased. These biochemical findings were supported by a histopathological examination of kidney tissues, which showed that in the animals that received a high dose of n-ZnO, numerous kidney glomeruli underwent atrophy and fragmentation. Moreover, the renal tubules showed epithelial desquamation, degeneration and necrosis. Some renal tubules showed casts in their lumina. Severe congestion was also observed in renal interstitium. These effects were dose dependent. Cotreatment of rats with Qur and/or Arg along with n-ZnO significantly improved most of the deviated tested parameters.

Conclusions

The data show that Qur has a beneficial effect against n-ZnO oxidative stress and related vascular complications. Also, its combination with Arg proved to be even more effective in ameliorating nano zinc oxide nephrotoxicity.     

Protective role of curcumin in nephrotoxic oxidative damage induced by vancomycin in rats

Vancomycin (VAN) is a glycopeptide antibiotic which is active against gram positive bacteria including methicillin resistant Staphylococci. Free radicals are involved in the pathogenesis of vancomycin-induced nephrotoxicity. Therefore, the present study was conducted to investigate the antioxidant potential of curcumin (CUR) against the nephrotoxicity of vancomycin in male rats. Animals used in this study were divided into four groups; the first group was used as control, the second, third and fourth groups were treated orally with curcumin (200 mg/kg BW/day), vancomycin (200 mg/kg BW/day, i.p.), vancomycin plus curcumin, respectively. Curcumin was administered 2 weeks before and 1 week simultaneously with vancomycin. Results showed that thiobarbituric acid reactive substances (TBARS) in plasma and kidney tissue were significantly increased after vancomycin administration. While, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in plasma and kidney tissue and the content of glutathione (GSH) in kidney tissue were decreased compared to control. Vancomycin significantly increased the levels of urea and creatinine. The presence of curcumin with vancomycin caused reduction in induction levels of TBARS in plasma and kidney, urea and creatinine. It ameliorated vancomycin-induced decrease in the activities of antioxidant enzymes and GSH. The presence of curcumin with vancomycin alleviated its nephrotoxic effects. It can be concluded that curcumin has beneficial influences and could be able to antagonize vancomycin nephrotoxicity.     

Liquorice plant extract reduces ochratoxin A-induced nephrotoxicity in rats

To evaluate the protective effect of liquorice plant extract (LPE) on ochratoxin A-induced nephrotoxicity, rats were exposed to ochratoxin A for 28 consecutive days. Biochemical analyses showed that ochratoxin A elevated the serum level of creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransaminase (ALT), and malondialdehyde (MDA) while antioxidant power of the serum was diminished significantly (P<0.05). Histopathological examinations revealed degenerative symptoms in proximal tubules, congestions in renal tissue, and a remarkable infiltration of the inflammatory cells as signs of ochratoxin A nephrotoxicity. Moreover, total antioxidant power of the serum and MDA generation was increased. The test compounds melatonin (MLT) and LPE alleviated most of the biochemical alterations. The results of the histopathological investigations of the kidneys supported these findings confirming the protective effects of the test compounds albeit with some differences in antioxidant potency. Taken together, our data may suggest that LPE like MLT could alleviate an ochratoxin A-reduced antioxidant power of serum and lower the toxin-induced MDA generation. Hence LPE might be considered as a practically antioxidant compound that may be beneficial in the prevention and treatment of ochratoxicosis.     

Reversal of cadmium-induced oxidative stress in rat erythrocytes by selenium,zinc or their combination

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced oxidative stress in erythrocytes, compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups received either 200 ppm Cd (as CdCl₂), 200 ppm Cd+500 ppm Zn (as ZnCl₂), 200 ppm Cd+0.1 ppm Se (as Na₂SeO₃), or 200 ppm Cd+500 ppm Zn+0.1 ppm Se in their drinking water for 35 days. Marked alterations of antioxidative system were found in Cd-treated rats. Activities of catalase (CAT) and glutathione peroxidise (GSH-Px) as well as the total glutathione (GSH) contents in erythrocytes were significantly decreased, whereas the activity of total superoxide dismutase (SOD) was significantly increased. The treatment of Cd-exposed rats with Se alone had no significant effect on the Cd-induced increase in the SOD activity but increased significantly the CAT and GSH-Px activities and partially reversed Cd-induced depletion of GSH levels in erythrocytes. The treatment of Cd-exposed animals with Zn alone partially reversed Cd-induced increase in SOD activity and Cd-induced decrease in GSH-Px activity. The combined treatment of Cd-exposed animals with Se and Zn was more effective than that with either of them alone in reversing Cd-induced decrease in CAT and GSH-Px activities and Cd-induced increase in SOD activity. This treatment also partially restored Cd-induced depletion of GSH. These results could be important for the further development of better treatments for people and/or animals exposed to Cd.     

Co-supplementation of single and multi doses of vitamins C and E ameliorates cisplatin-induced acute renal failure in mice

Higher doses of antioxidant vitamins C and E have been proved to be effective against cisplatin-induced nephrotoxicity in animals. However, the possible effective equivalent dose in human was found to be higher than that of the upper tolerable intake level (UL) for these vitamins. Hence, the current study was aimed to evaluate the protective effect of co-supplementation of single and multi doses of vitamins C and E against cisplatin-induced acute renal failure in mice. Single dose of vitamin C (500 mg/kg), vitamin E (500 mg/kg), and vitamin C plus vitamin E (250 mg/kg each) were administered orally 1 h prior to cisplatin (12 mg/kg, i.p) injection, whereas in a multidose study they were administered 1 h prior, and 24 and 48 h after the cisplatin injection. Serum urea and creatinine levels were estimated 72 h after the injection of cisplatin. Renal concentrations of glutathione (GSH) and malondialdehyde (MDA) were also determined. Co-supplementation of vitamins significantly protected the cisplatin-induced increased levels of serum urea, creatinine, renal MDA, and the declined renal GSH level. Administration of single and multi doses of vitamin C plus E (250 mg/kg each) rendered significant nephroprotection. Therefore, accounting for the rare side effect from high intake of vitamins C and E observation of this study indicates that a multidose combination therapy of these vitamins at their lower doses can be effective in protecting the cisplatin-induced renal damage. The protection is partially mediated through the antioxidant effect of the vitamins.     

Therapeutic effect of cimetidine on acetaminophen-induced nephrotoxicity in rats

Acetaminophen as an analgesic and antipyretic drug can induce renal toxicity in high doses. Cimetidine as an H₂-blocker can inhibit the cytochrome P450 enzymes and reduce the toxic effect of acetaminophen on renal tissue. Eighty rats in eight groups comprising normal control group, acetaminophen control group, cimetidine control group, and five different treatment groups (cimetidine was administrated at 0, 1, 2, 4, and 8 h after acetaminophen administration) were used. Acetaminophen was administered at a toxic of dose 3 g/kg orally, and cimetidine (12.5 mg/kg) was administrated by intraperitoneal route at different times after induction of toxicity. Creatinine and urea were measured, and pathologic lesions were determined. In treatment groups 3 and 6, the urea and creatinine concentration showed no significant difference from group 1. In other treatment groups, the urea and creatinine concentrations were increased significantly (p < 0.05). Histopathologic changes in group 6 were mild in comparison to other groups. We concluded that administration of cimetidine at least 2 h after acetaminophen toxicity can reduce renal lesions.