Renal Toxicity In Rats Research Articles

Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment

The aim of this study was to investigate whether thymoquinone (TQ) could alleviate diclofenac (DCLF)-induced gastrointestinal and renal toxicity in rats. Diclofenac was administered via intramuscular injection twice daily for 5 days and TQ was given by gavage for the same period. Hematological and biochemical profiles were measured with autoanalyzers while reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Tissue injuries were evaluated by microscopy and histopathological scoring. Diclofenac treatment caused kidney and liver function test abnormalities, reduced hematocrit and hemoglobin levels but increased WBC and platelet counts. Histopathological findings showed renal tubular damage, gastrointestinal lesions and increased fibrosis in DCLF treated rats. Thymoquinone administration, along with DCLF treatment, attenuated hematological test abnormalities and DCLF induced renal functional impairment as evident by significantly restored serum creatinine and blood urea nitrogen levels. Similarly, TQ treatment significantly alleviated liver function test abnormalities and decreased tissue injury in the stomach and duodenum. Diclofenac treatment caused increased ROS/RNS formation and decreased TAC in the kidney, stomach and duodenal tissue. Thymoquinone administration increased gastrointestinal and renal TAC in DCLF treated rats. These results indicate that TQ could ameliorate gastrointestinal and renal toxicity induced by high dose DCLF treatment.

Protective Effect of Ixora Coccinea Flowers against Cadmium Chloride induced Nephrotoxicity Model in Rats

The present study was carried out to evaluate the protective effects of the aqueous extract of Ixora coccinea flowers (AICF) against CdCl2 induced renal toxicity in rats. The study was performed using 30 (rats), divided into five groups i.e control group, CdCl2 treated group and plant extract at a dose of 100, 200 and 400 mg/kg body weight along with CdCl2 treated groups. The exposure to CdCl2 exhibit marked destruction in kidney function characterized by decrease in the body weight, increase in kidney weight and increase in serum creatinine, urea and uric acid levels, decrease of total protein levels and histopathological variations. The pretreatment of AICF at a dose of 100, 200 and 400 mg/kg body weight for eight days significantly improved the various biochemical parameters in a dose dependent manner. Furthermore, the histological alterations were also ameliorated by AICF. The AICF showed apparent dose dependent proactive effect on CdCl2 induced nephrotoxicity model in rats.

Histocytoarchitectural Changes of Wistar Rat’s Kidney Exposed to Young Coconut Water Before and After Induction with Carbon Tetrachloride

Background: Young coconut water (YCW) has been used by individuals to boast immunity and that of the experimental animals. In this study an attempt was made to investigate the protective effect of YCW against the Carbon tetrachloride (CCl4) induced renal toxicity in rats. Methods: A total of 20 male adult wistar rats which were not previously subjected to any experiment were divided into four groups. Each group has five rats. Group 1 (Normal control) received basal diet, olive oil and water. Group 2 (Positive control) received basal diet, olive oil and YCW (100ml/kg). Group 3 (Negative control) received basal diet, water and CCl4 diluted with water and olive oil. Group 4 (Experimental group) received basal diet and YCW (100ml/kg) and then intoxicated with CCl4 diluted with water and olive oil. After day 7, the rats were sacrificed and their kidneys were collected and processed histologically following standard protocols. Results: Group 1 (Normal control) displayed normal histocyto-archetature of the kidney. Group 2 (Positive control) revealed hyperplasia with mild inflammatory response. Group 3 (Negative control) showed hyper-cellularity, mild cystic spaces, necrosis, and loose glomerular membrane indicative of high inflammatory response. Group 4 (Experimental group) revealed moderate cellular activities in line with moderate inflammatory response. Conclusion: The administration of YCW on the rat before intoxication with CCl4 suppresses the deleterious effect of CCl4 on the experimental group.

Protective Effects of Fragaria ananassa Extract Against Cadmium Chloride-Induced Acute Renal Toxicity in Rats.

For experiments of cadmium toxicity in animal models, cadmium (II) chloride is often used due to its solubility in water and its ability to produce high concentrations of cadmium at the target site. The present study was designed to investigate the potential inhibitory effect of the Fragaria ananassa fruit extract on cadmium (II) chloride-induced renal toxicity in rats. Tested animals were pretreated with the extract of F. ananassa and injected with cadmium (II) chloride (6.5-mg/kg body weight) for 5days. Cadmium (II) chloride significantly increased kidney cadmium concentration, kidney weight, lipid peroxidation, and nitric oxide production. Plasma uric acid, urea, and creatinine levels also increased significantly, indicative of kidney dysfunction. These effects were accompanied by significantly decreased levels of nonenzymatic and enzymatic antioxidant molecules (i.e., glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Moreover, messenger RNA (mRNA) expression of the antiapoptotic protein, Bcl-2, and the antioxidant proteins, superoxide dismutase 2 and glutathione reductase, were downregulated markedly, whereas mRNA expression of tumor necrosis factor-α was upregulated significantly in kidney tissues of cadmium-treated rats. Histology of kidney tissue demonstrated severe, adverse changes that reflected cadmium-induced tissue damage. Pretreatment of rats with the extract of F. ananassa ameliorated all aforementioned cadmium (II) chloride-induced changes. In conclusion, the present study showed acute renal toxicity in rats treated with cadmium (II) chloride. The study also revealed that pretreatment with the extract of F. ananassa could protect the kidney against cadmium (II) chloride-induced acute renal toxicity.

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Effect of vitamin E on biochemical and ultrastructural changes in acrylamide-induced renal toxicity in rats

<p class="abstract"><strong>Background:</strong> Acrylamide (ACR) is a widely used chemical in industry and it accounts for major health problems as it has been detected in highly consumed food items, carbohydrate-rich food items cooked at high temperature. Accordingly the population is highly exposed to ACR. The aim of the study was to assess the effect of vitamin E on biochemical and ultrastructure changes in acrylamide-induced renal toxicity in wistar albino rats.</p><p class="abstract"><strong>Methods:</strong> Three groups of adult albino wistar rats weighing about (200-250 gm) were used in this study to investigate the effect of vitamin E on acrylamide induced renal toxicity; 10 rats in each group; Group I: Control group, Group II: Acrylamide treated and Group III: Acrylamide-Vit E treated group. Blood samples were collected for estimation of serum creatinine, blood urea nitrogen (BUN), lactic dehydrogenase (LDH) and albumin. Kidneys specimens were processed for light and electron microscopic studies. Kidney sections were stained with H&E, MT, PAS and immuno-histochemical stains for detection of NF-kβp65 and Bcl-2. Morphometric study was done followed by biochemical and morphometric statistical analysiss.</p><p class="abstract"><strong>Results:</strong> Acrylamide treated rats showed degeneration of cells lining PCT and DCT, atrophy of glomeruli and fibrosis. Ultrastructurally; tubules lining cells showed loss of microvilli, basal membrane in foldings and mitochondrial changes. Podocytic changes include: Vacuolation, irregularity and disorientation of their processes and thinning of glomerular basement membrane. Significant increase in the mean number of NF-kβp65 positive cells and decrease in the mean area% of Bcl-2 immuno-expression, increase in the mean area % of collagen fibers and urinary space diameter and decrease in thickness of epithelial cells of PCT and DCT were also observed. Serum creatinine, BUN anLDH were increased whereas serum albumin was decreased. Vitamin E co-administration with ACR improve all these histological, ultrastructural and biochemical changes.</p><strong>Conclusions:</strong> Acrylamide induced renal toxicity could be ameliorated by vitamin E co-administration.

Hepato- and nephroprotective effects of bradykinin potentiating factor from scorpion (Buthus occitanus) venom on mercuric chloride-treated rats.

Bioactive peptides such as bradykinin potentiating factor (BPF), have, anti-oxidative, anti-inflammatory, immunomodulatory and ameliorative effects in chronic diseases and play a potential role in cancer prevention. It is known that the liver and kidney accumulate inorganic mercury upon exposure, which often leads to mercury intoxication in these organs. In this study, we investigated the effect of bradykinin potentiating factor (BPF), a scorpion venom peptide, on mercuric chloride-induced hepatic and renal toxicity in rats. We used 20 adult male Albino rats divided into four equal groups: the first group was injected with saline (control); the second group was administered daily with mercuric chloride (HgCl2) for 2 weeks; the third group was administered with BPF twice weekly for 2 successive weeks, while the fourth group was exposed to BPF followed by HgCl2. We observed that HgCl2 treated rats had a significant increase in serum ALT, AST, ALP, creatinine and urea levels compared to control. Furthermore, HgCl2 treated rats showed a marked decrease in total proteins, albumin and uric acids compared to control. The previously studied parameters were not significantly changed in BPF pretreated rats compared to control. Moreover, a significant decrease in the activities of glutathione perioxidase (GSH), superoxide dismutase (SOD), and catalase (CAT), in addition to a significant increase in the level of malondialdehyde (MDA) were observed in hepatic and renal tissues of rats after HgCl2 treatment. In contrast, the HgCl2/BPF treated rats showed a significant elevation in the activity of GSH, SOD, and CAT accompanied with a significant regression in the level of MDA compared to the HgCl2 exposed rats. We conclude that treatment with BPF is a promising prophylactic approach for the management of mercuric chloride-induced hepato- and nephro-toxicities.

Design, synthesis, evaluation and molecular modelling studies of some novel 5,6-diphenyl-1,2,4-triazin-3(2H)-ones bearing five-member heterocyclic moieties as potential COX-2 inhibitors: A hybrid pharmacophore approach

A series of novel hybrids comprising of 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole tethered to 5,6-diphenyl-1,2,4-triazin-3(2H)-one were designed, synthesised and evaluated as COX-2 inhibitors for the treatment of inflammation. The synthesised hybrids were characterised using FT-IR, 1H NMR, 13C NMR, elemental (C,H,N) analyses and assessed for their anti-inflammatory potential by in vitro albumin denaturation assay. Compounds exhibiting activity comparable to indomethacin and celecoxib were further evaluated for in vivo anti-inflammatory activity. Oral administration of promising compounds 3c–3e and 4c–4e did not evoke significant gastric, hepatic and renal toxicity in rats. These potential compounds exhibited reduced malondialdehyde (MDA) content on the gastric mucosa suggesting their protective effects by inhibition of lipid peroxidation. Based on the outcome of in vitro COX assay, compounds 3c–3e and 4c–4e (IC50 0.60–1.11μM) elicited an interesting profile as competitive selective COX-2 inhibitors. Further, selected compounds 3e and 4c were found devoid of cardiotoxicity post evaluation on myocardial infarcted rats. The in silico binding mode of the potential compounds into the COX-2 active site through docking and molecular dynamics exemplified their consensual interaction and subsequent COX-2 inhibition with significant implications for structure-based drug design.

Folic Acid and Grape Seed Extract Prevent Azathioprine-induced Fetal Malformations and Renal Toxicity in Rats.

Azathioprine (AZA) is an important drug commonly used in the therapy of the autoimmune system disorders. It induces many hazard effects that restrict its use. The present study was designed to investigate the influence of AZA on the fetal development and renal function and its co-administration with either folic acid (FA) or grape seed extract (GSE). The effects of administration of GSE or FA on AZA toxicity by gavage simultaneously for 4 weeks were studied by determining the changes in kidney histology, the glutathione level (GSH), and lipid per oxidation content as malondialdehyde in the kidney tissue. Additionally, their effects on the fetal development were investigated. Azathioprine induced a renal damage as indicated from the pronounced changes in histological structure, a significant increase in serum urea and creatinine, and malondialdehyde content in the kidney tissue. Meanwhile, the GSH activity was significantly decreased. Co-treatment with GSE significantly minimized the previously mentioned hazard effects of AZA by ameliorating the antioxidant activity. At this point, FA induced a nonsignificant protective activity. The results also revealed that administration of FA or GSE at 6th to 15th day of gestation did not altered fetal development. While, AZA administration clearly disturbed fetal development as indicated from a significant decrease in fetal weights. Furthermore, co-administration of both drugs significantly minimized similarly the hazards of AZA on the fetal development. It may be concluded that GSE and FA are a useful remedies. Maternal administrations of either both are protective agents against AZA-induced fetal malformations. Grape seed extract was more active than FA in potentiating the antioxidative defenses for controlling AZA-induced oxidative renal damages. Copyright © 2016 John Wiley & Sons, Ltd.

Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd) and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6): saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05). However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes) and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO). However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

Proficiencies of Artemisia scoparia against CCl4 induced DNA damages and renal toxicity in rat.

BackgroundArtemisia scoparia is traditionally used in the local system of medicine in kidney disorders. This study aimed at scrutinizing the nephroprotective prospective of A. scoparia methanol extract against carbon tetrachloride (CCl4) provoked DNA damages and oxidative stress in kidneys of rat.MethodsDried aerial parts of A. scoparia were powdered and extracted with methanol to obtain the viscous material (ASM). Sprague Dawley male rats (42) were grouped (7) having 6 rats in each. Group I remained untreated and Group II treated intraperitoneally (i.p) with DMSO + olive oil (1 ml/kg body weight (bw). Rats of Group III - VI were treated with CCl4 (1 ml/kg bw; i.p 30 % v/v in olive oil). Animals of Group IV were co-administered with 100 mg/kg bw of silymarin whereas rats of Group V and VI with 150 mg/kg bw and 300 mg/kg bw of ASM at an interval of 48 h for four weeks. Animals of Group VII were administered with ASM (300 mg/kg bw) alone. DNA damages were investigated with comet assay in renal tissues while the oxidative injuries were estimated in serum and renal tissues.ResultsCo-administration of ASM to rats significantly reduced the DNA damages at 300 mg/kg dose as indicated in comet length (40.80 ± 2.60 μm), head length (34.70 ± 2.21 μm), tail length (7.43 ± 1.24 μm) and DNA content in head (88.03 ± 2.27 %) to that of CCl4 for comet length (63.16 ± 2.11 μm), head length (23.29 ± 1.50 μm), tail length (39.21 ± 2.81 μm) and DNA content of head (74.81 ± 2.18 %) in renal cell’s nuclei. Increased level of urea, creatinine, bilirubin, blood urea nitrogen whereas decreased concentration of proteins in serum of CCl4 treated animals were restored towards the normal level with co-administration of ASM. CCl4 injection in rats decreased the activity level of CAT, POD, SOD, GST and γ-GT and GSH contents while elevated levels of TBARS, H2O2 and nitrite contents were observed in renal tissues. A noteworthy retrieval of all these parameters and the altered histopathological observations was notified near to the normal values after treatment with both the doses of ASM.ConclusionResults obtained suggested the therapeutic role of ASM in oxidative stress related disorder of kidneys.

Studying the protective effect of gamma-irradiated basil (Ocimum basilicum L.) against methotrexate-induced liver and renal toxicity in rats

The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe hepatic and renal toxicity. Basil has shown antioxidant and antimicrobial activities due to its phenolic and aromatic compounds. Here, the aim of this work was to investigate the effect of g-radiation processing on the total phenolic and total flavonoids content of dried basil as well as to study the protective role of g-irradiated dried basil leaves against MTX-induced hepatic and renal toxicity in rats. Results obtained that g-radiation treatment increased the amount of total phenolic and total flavonoids content of dried basil. Additionally, the results demonstrated that the MTX (in saline, 20 mg/kg) given to rats on the day 21 of the experiment resulted in significant elevation in the activities of serum alanine and aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and the levels of serum urea, creatinine and uric acid as well as the concentration of hepatic and renal malondialdehyde and xanthine oxidase accompanied with a depression in hepatic glutathione content and xanthine dehydrogenase, superoxide dismutase and catalase activities in comparison with control and treated groups. Addition of either raw or g-irradiated basil (1%) to the diet of MTX-rats has significantly reduced the activities of serum enzymes and the levels of serum urea, creatinine and uric acid accompanied by ameliorating the alteration in the antioxidant/oxidant status of the liver and kidney. It was concluded that basil can protect against MTX-induced hepatic and renal injury and may be of therapeutic potential in alleviating the systemic side effects of this chemotherapeutic agent.

Ameliorative effect of &lt;i&gt;Aegle marmelos&lt;/i&gt; leaves extract against cisplatin-induced nephrotoxicity and oxidative stress

&lt;p class="Abstract"&gt;The methanolic extract of &lt;em&gt;Aegle marmelos&lt;/em&gt; leaves was evaluated against cisplatin-induced renal toxicity in rats. Rats were divided into 5 groups: Group 1 received normal saline (1 mL, p.o.) for 15 days; Group II received single dose of cisplatin (5 mg/kg, i.p.) on day 15 and normal saline (1 mL, p.o.) for 15 days; Group III, IV and V were pretreated with extract at doses of 100, 300, 600 mg/kg, p.o., respectively for 15 days followed by single dose of cisplatin on day 15. The blood was collected on the day 16. The urea, creatinine, uric acid, sodium, potassium levels in the serum/blood and TBARS, reduced glutathione (GSH), sueroxide dismutase, catalase in tissue homogenate of kidneys were analyzed. The extract at all doses significantly ameliorated the changes in the serum parameters and decreased the elevated level of TBARS and increased the reduced level of GSH, sueroxide dismutase, catalase. The &lt;em&gt;A. marmelos&lt;/em&gt; extract was found to possess nephroprotective and anti-oxidant activities.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

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Beneficial effects of carnosine and carnosine plus vitamin E treatments on doxorubicin-induced oxidative stress and cardiac, hepatic, and renal toxicity in rats.

Oxidative stress plays an important role in doxorubicin (DOX)-induced toxicity. Carnosine (CAR) is a dipeptide with antioxidant properties. The aim of this study was to evaluate the decreasing or preventive effect of CAR alone or combination with vitamin E (CAR + Vit E) on DOX-induced toxicity in heart, liver, and brain of rats. Rats were treated with CAR (250 mg kg(-1) day(-1); intraperitoneally (i.p.)) or CAR + Vit E (equals 200 mg kg(-1) α-tocopherol; once every 3 days; intramuscularly) for 12 consecutive days. On the 8th day of treatment, rats were injected with a single dose of DOX (30 mg kg(-1), i.p.). Serum cardiac troponin I (cTnI), urea, and creatinine levels; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities; and oxidative stress parameters in tissues were measured. We also determined thiobarbituric acid reactive substances, diene conjugate, protein carbonyl (PC), and glutathione levels and antioxidant enzyme activities. DOX resulted in increased serum cTnI, ALT, AST, urea, and creatinine levels and increased lipid peroxide and PC levels in tissues. CAR or CAR + Vit E treatments led to decreases in serum cTnI levels and ALT and AST activities. These treatments reduced prooxidant status and ameloriated histopathologic findings in the examined tissues. Our results may indicate that CAR alone, especially in combination with Vit E, protect against DOX-induced toxicity in heart, liver, and kidney tissues of rats. This was evidenced by improved cardiac, hepatic, and renal markers and restoration of the prooxidant state and amelioration of histopathologic changes.

Toxicokinetics of bakuchiol,hepatic and renal toxicity in rats after single oral administration of Psoraleae Fructus and combination with Glycyrrhizae Radix et Rhizoma

To study the toxicokinetics of bakuchiol, hepatic and renal toxicity in rats after single oral administration of Psoraleae Fructus and combined with Glycyrrhizae Radix et Rhizoma, in order to provide scientific evidences for clinical safe medication use. A total of 35 SD rats were randomly divided into seven groups: vehicle (distilled water) control group, Glycyrrhizae Radix et Rhizoma group, positive control (aristolochic acid A) group, Psoraleae Fructus (40 g x kg(-1)) group( both male and female rats), Psoraleae Fructus and Glycyrrhizae Radix et Rhizoma (40 +20) g x kg(-1) group (both male and female rats). HPLC-UV method was used to determine the concentration of bakuchiol in rat plasma at different time points after single oral administration. Plasma alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), plasma creatinine (Cr), N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule 1 (Kim-1) were measured after administration for 24 h. The main toxicokinetics parameters of bakuchiol in rats exert significantly gender difference. When Psoraleae Fructus combination with Glycyrrhizae Radix et Rhizoma, the total area under the plasma concentration-time curve( AUC), C(max), and plasma clearance (CL) of bakuchiol were increased, respectively; CL, half-life (t½) were decreased, and T(max) were prolonged. The biochemical indicators (including ALT, AST, BUN, Cr and KIM-1 level) in different dose of Psoraleae Fructus groups, were found no statistically significant difference when compared with vehicle control group. The level of NAG in both Psoraleae Fructus and compatibility with Glycyrrhizae Radix et Rhizoma groups were significant increased (P < 0.05). There are obvious effects on toxicokinetics of bakuchiol in rats when Psoraleae Fructus combined with Glycyrrhizae Radix et Rhizoma. Renal toxicity induced by Psoraleae Fructus at high dose was observed after single oral administration and no liver damage in rats was found.

Hepato- and nephrotoxicity in male albino rats exposed to malathion and spinosad in stored wheat grains.

Adult male albino rats were fed on stored wheat grains (Triticum aestivum L.) treated with malathion and spinosad at both 8 and 16 ppm for 90 consecutive days to evaluate their hepatic and renal toxicity. The activity of serum acetylcholinesterase (AChE) was decreased in rats treated with the higher concentration of both tested pesticides. Biochemical parameters of liver functions [i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), acid phosphatase (ACP) activity, as well as total protein, albumin, bilirubin and cholesterol levels] were severely affected especially at higher concentration. Malathion and spinosad elevated the activity of ALT, AST, ALP and ACP in rats treated with the higher concentration. Also, total and direct bilirubin levels increased in rats treated with the higher concentration of both pesticides. On the contrary, both pesticides decreased total protein and albumin levels in treated rats in a concentration-dependent manner. Furthermore, malathion was found to be hyperglycemic. Kidney function parameters (i.e., urea and creatinine levels) were increased in treated rats in a concentration-dependent manner. The above mentioned effects were supported by histopathological examination of liver and kidney tissues. The obtained results indicated also that malathion was able to cause a more pronounced hepato- and renal toxicity in rats than spinosad.

Effect of olive leaf extract treatment on doxorubicin-induced cardiac, hepatic and renal toxicity in rats

Doxorubicin (DOX) is known to increase in oxidative stress in several organs. Olive leaf extract (OLE) has potent antioxidant effects; therefore, we evaluated the ability of OLE to reduce DOX-induced toxicity in the heart, liver, and kidneys of rats. DOX (30mg/kg; i.p.) was administered to rats, which were sacrificed 4 days after DOX. The rats received OLE (6 and 12mL/L in drinking water) for 12 days. Serum cardiac troponin I (cTnI) levels, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, urea and creatinine levels, as well as prooxidant and antioxidant status in organs were measured. DOX was found to increase serum markers that indicate tissue injury, malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) levels, and to decrease glutathione (GSH) levels in organs. Histopathologic changes were also evaluated. OLE, especially OLE 1000, led to decreases in serum cTnI and urea levels, ALT and AST activities, and amelioration in histopathologic findings. Decreases in MDA, DC, and PC, and increases in GSH levels were observed in organs of DOX-treated rats due to OLE. We conclude that OLE treatment may be effective in decreasing DOX-induced cardiac, hepatic and renal oxidative stress and injury.

Crocin Abrogates Carbon Tetrachloride-Induced Renal Toxicity in Rats via Modulation of Metabolizing Enzymes and Diminution of Oxidative Stress, Apoptosis, and Inflammatory Cytokines.

This work aimed at investigating the potential modulatory effects and mechanisms of crocin against CCl4 -induced nephrotoxicity. Forty male rats were allocated for three weeks treatment with corn oil, CCl4 , crocin, or crocin plus CCl4 . Crocin effectively mitigated CCl4 -induced kidney injury as evidenced by amelioration of alterations in kidney histopathology, renal weight/100 g body weight ratio and kidney functions. Crocin modulated CCl4 -induced disturbance of kidney cytochrom-P450 subfamily 2E1 and glutathione-S-transferase. The attenuation of crocin to kidney injury was also associated with suppression of oxidative stress via reduction of lipid peroxides along with induction of renal glutathione content and enhancement of superoxide dismutase, glutathione peroxidase, and catalase activities. Crocin mitigated CCl4 -induced elevation of the renal levels of tumor necrosis factor-alpha, interleukin-6, prostaglandin E2, and active caspases-3. Collectively, crocin alleviated CCl4 -induced renal damage via modulation of kidney metabolizing enzymes, suppression of oxidative stress, inhibition of inflammatory cytokines, PGE2, and active caspase3 in kidney.

Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity.

Aluminum has toxic potential on humans and animals when it accumulates in various tissues. It was shown in a number of studies that aluminum causes oxidative stress by free radical formation and lipid peroxidation in tissues and thus may cause damage in target organs. Although there are numerous studies investigating aluminum toxicity, biochemical mechanisms of the damage caused by aluminum have yet to be explained. Melatonin produced by pineal gland was shown to be an effective antioxidant. Since kidneys are target organs for aluminum accumulation and toxicity, we have studied the role of melatonin against aluminum-induced renal toxicity in rats. Wistar albino rats were divided into five groups. Group I served as control, and received only physiological saline; group II served as positive control for melatonin, and received ethanol and physiological saline; group III received melatonin (10mg/kg); group IV received aluminum sulfate (5mg/kg) and group V received aluminum sulfate and melatonin (in the same dose), injected three times a week for 1month. Administration of aluminum caused degenerative changes in renal tissues, such as increase in metallothionein immunoreactivity and decrease in cell proliferation. Moreover, uric acid and lipid peroxidation levels and xanthine oxidase activity increased, while glutathione, catalase, superoxide dismutase, paraoxonase 1, glucose-6-phosphate dehydrogenase, and sodium potassium ATPase activities decreased. Administration of melatonin mostly prevented these symptoms. Results showed that melatonin is a potential beneficial agent for reducing damage in aluminum-induced renal toxicity.