Cisplatin In Male Rats Research Articles

Ameliorative effects of Ellagic acid against toxicity of cisplatin in male rats

Ameliorative effects of Ellagic acid against toxicity of cisplatin in male rats

Impact of ginseng on neurotoxicity induced by cisplatin in rats.

Over the years, many researches have shown the potential protective effects of ginseng for preventing and treating neurological damage and their related diseases. Neuronal disturbance is one of the most common serious effects of cisplatin chemotherapy that triggers memory impairment and cognitive disability. Based on the hypothesis that mechanistic pathways of ginseng against the neurological and biochemical disturbance remain unclear, therefore, this study was designed to investigate the neuroprotective effect of ginseng extract against neurological and behavior abnormality induced by cisplatin in male rats. Animals were divided into 4 groups. Group 1 served as a control, group 2 was orally administrated with ginseng (100 mg/kg BW) daily for 90 days, group 3 was injected intraperitoneally with cisplatin (4 mg/kg BW) once a week for 90 days, and group 4 received ginseng and cisplatin. Cisplatin induced a learning and memory dysfunction in the Morris water maze task and locomotor disability in the rotarod test. In addition, cisplatin disrupted the oxidant/antioxidant systems, neuroinflammatory molecules (TNF-α, IL-6, IL-12, and IL-1β), neurotransmitters, and apoptotic (caspase-3, P53, and Bax) and dementia markers (amyloid-β40 and amyloid-β 42). Co-treatment with ginseng extracts successfully ameliorated the cognitive behaviors and intramuscular strength and presented a good protective agent against neurological damage. Histopathological and histochemical studies proved the neuroprotective effect of ginseng. Our data showed that ginseng capable to counteract the memory dysfunction is induced by cisplatin via reducing oxidative stress and neuroinflammation restoring the neurological efficiency.

Potential Protective Effect Of Quercetin Against Cisplatin-Induced Acute Nephrotoxicity In Male Rats

Cisplatin-induced nephrotoxicity is a significant dose limiting side effect. We investigated the possible nephroprotective effect of quercetin before and after inducing acute renal damage using cisplatin in male rats. Cisplatin administration resulted in renal damage represented by the elevated renal function parameters, elevated oxidative stress and inflammatory markers, and diminished production of the antioxidant marker. Treatment with quercetin showed reduced levels of renal function parameters, improved antioxidant status, and reduced levels of MDA and TNF-α. This study revealed a potential role of quercetin in protection against cisplatin-induced nephrotoxicity.

Melissa of cinalis and Vitamin E as the Potential Therapeutic Candidates for Reproductive Toxicity Caused by Anti-cancer Drug, Cisplatin, in Male Rats.

High doses of Cisplatin (CP) can disrupt the normal functioning of various tissues such as ovaries and testis. In almost all the patients, spermiotoxicity of CP causes temporary or permanent azoospermia. In this study, the defensive effect of Melissa of cinalis and vitamin E against testicular injuries caused by CP in male rats was evaluated. Thirty six male rats were distributed into 6 groups. Group 1 was used as the negative control. In group 2, a single dose of CP (10 mg/kg) was administered on the first day. In groups 3 and 4, a single dose of CP (10 mg/kg) was administered on the first day and then treated with Melissa of cinalis at 1000 mg/kg/day and vitamin E at 100 mg/kg/day for 7 consecutive days, respectively. Groups 5 and 6 were treated with Melissa of cinalis and vitamin E for 7 consecutive days, respectively. After euthanasia, serum levels of testosterone, Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) were evaluated. Testes were removed and weighed. Spermatic analysis was done on the tail of the epididymis. Tissue lipid peroxidation and activity of antioxidant enzymes in testes were evaluated as well. The results showed that Melissa of cinalis and vitamin E increased serum levels of testosterone, LH and FSH, weight of testes and sperm motility, count and vitality and decreased sperm cell abnormalities in rats given CP. Our results are useful in designing a medication of Melissa of cinalis that can protect the testes against CP-induced testicular damage and infertility in cancerous male patients.

Abrogation by Curcumin on Testicular Toxicity Induced by Cisplatin in Rats

Cisplatin is one of the most effective and widely-used antineoplastic agents for the treatment of testicular germ cell tumors. The present study was conducted to examine the possible modifying effects of curcumin against testicular toxicity induced by cisplatin in male rats. 60 male albino rats were equally divided into six groups; the first and second groups were the control and curcumin treated group respectively while the 3rd group was cisplatin treated group; the 4th and 5th groups were co- and post treated cisplatin rat with curcumin respectively and the 6th group was self treated cisplatin rat group. Many side effects were observed in animals injected with cisplatin such as loosing of body weight, loss of activity, weakness, yellowish body hair. A significant decrease in the body and testicular weights,, sperm counts, sperm motility, plasma testosterone, luteinizing hormone reduced glutathione, total antioxidant capacity, and total protein levels in cisplatin and cisplatin self treated groups when compared with the control group. On the other hand; a significant increase in the MDA and NO in cisplatin and cisplatin self treated groups when compared with the control group. sperm count and sperm motility, GSH and TAC exhibited significant increased in cisplatin treated with curcumin when compared with cisplatin groups, moreover, sperm abnormality, MDA, NO and total protein exhibited significant decrease in cisplatin treated groups with curcumin when compared with cisplatin groups. A significant decrease in sperm abnormality, MDA, NO and total protein and a significant increase in GSH and TAC in Co-treated group when compared with post treated cisplatin with curcumin. Our recommendation, administration of curcumin caused ameliorative effect against cisplatin-induced testicular toxicity.

Efficacy of Ganoderma ( Ganoderma lucidum ) Against Nephrotoxicity Induced by Cisplatin in Male Rats

In traditional Chinese medicine, ganoderma lucidum are widely used as medicine for a variety of diseases, such as chronic bronchitis inflammation, hyperlipidemia, hypertension, neurasthenia, hepatitis, leukopenia, and adjuvant treatment of cancer . The aim of this study was to evaluate its effect against cisplatin - induced nephrotoxicity in adult male albino rats . Forty five animals were classified into 5 groups 9 rats for each group . Group (1) fed on basal diet (negative group); groups (2 - 5) were injected with cisplatin ( 5 mg / kg body wt. ) intraperitoneuly to induce nephrotoxicity in rats ; group ( 2 ) fed on the basal diet as positive control group (+Ve) ; remained groups fed on the basal diet and supplemented with ganoderma lucidum at 5 , 10 and 15 g / kg diet , respectively . Results revealed that positive control group had significant increase in serum levels of creatinine , urea , uric acid , urea nitrogen and total protein as well as Malondialdahyde ( MOD ) but had significant decrease in serum levels of Superoxide Dismutase (SOD) , Catalase (CAT) , Glutathione Peroxidase (GPX) and Glutathione (GSH) as compared to the negative control groups. While supplemented with different levels of ganoderma lucidum caused significant decreased in serum levels of creatinine , urea , uric acid , urea nitrogen and total protein as well as ( MOD ) , but had significant increased in serum levels of (SOD) , (CAT) , (GPX) and (GSH) as compared to the positive control group. From the present results it can be concluded that ganoderma lucidum feeding possess a therapeutic effect against cisplatin that induced nephrotoxicity in rats and inhibit oxidative stress. According to above results the consumption of ganoderma lucidum can be used to treat nephrotoxicity

Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats

Cisplatin is one of the most potent chemotherapeutic antitumor drugs. Oxidative stress has been proven to be involved in cisplatin-induced toxicity. Therefore, the present study was undertaken to examine the antioxidant potential of grape seed proanthocyanidin extract (GSPE) against the toxicity of cisplatin in male rats. Cisplatin treated animals revealed a significant elevation in plasma, heart, kidney and liver thiobarbituric acid reactive substances (TBARS), while the activities of antioxidant enzymes (GST, SOD, CAT and GSH-Px, and the levels of glutathione (GSH) were decreased. Aspartate and alanine transaminases (AST and ALT), creatine kinase and lactate dehydrogenase were significantly increased in plasma, while liver AST and ALT were significantly decreased. Cisplatin significantly increased the levels of plasma total lipid, cholesterol, urea and creatinine, and the relative weight of kidney. On the other hand, plasma total protein and albumin, and body weight were significantly decreased. GSPE reduced cisplatin-induced the levels of TBARS in plasma, heart, kidney and liver, TL, cholesterol, urea and creatinine, and liver AST and ALT. Moreover, it ameliorated cisplatin-induced decrease in the activities of antioxidant enzymes, and GSH, total protein and albumin. Therefore, the present results revealed that GSPE exerts a protective effect by antagonizing cisplatin toxicity.

Comparative effects of acute and subacute lycopene administration on chromosomal aberrations induced by cisplatin in male rats

Lycopene is a natural carotenoid, free radical scavenger, and presents protective effects by inhibiting oxidative DNA damage. The objective of the current study was to investigate the cytogenetic effects of a single acute and four daily gavage administrations of lycopene, and to examine possible protective effects on chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone marrow cells. The animals were divided into treatment groups, with three lycopene doses in the acute treatment (2, 4, and 6 mg/kg b.w.), three lycopene doses in the subacute treatment (0.5, 1.0, and 1.5 mg/kg b.w.) with and without cDDP (5 mg/kg b.w. i.p.), and respective controls. The results indicated that lycopene is neither cytotoxic nor clastogenic when compared with the negative controls ( p > 0.01). cDDP-treated animals submitted to acute and subacute treatments with different lycopene doses showed a significant reduction ( p < 0.01) in the number of abnormal metaphases when compared with the animals treated only with cDDP. The protective effects of lycopene on cDDP-induced chromosomal damage may be attributed to its antioxidant activity. These results suggest that this carotenoid may prove useful in reducing some of the toxic effects associated with certain classes of chemotherapeutic agents.

Association between tubular toxicity of cisplatin and expression of organic cation transporter rOCT2 (Slc22a2) in the rat

Cisplatin is an effective anticancer drug, but has its severe adverse effects, especially nephrotoxicity. The molecular mechanism of cisplatin-induced nephrotoxicity is still not clear. In the present study, we examined the role of rat (r)OCT2, an organic cation transporter predominantly expressed in the kidney, in the tubular toxicity of cisplatin. Using HEK293 cells stably expressing rOCT2 (HEK-rOCT2), we evaluated the cisplatin-induced release of lactate dehydrogenase and the uptake of cisplatin. The release of lactate dehydrogenase and the accumulation of platinum were greater in HEK-rOCT2 cells treated with cisplatin than in mock-transfected cells. Moreover, cimetidine and corticosterone, OCT2 inhibitors, inhibited the cytotoxicity and the transport of cisplatin in HEK-rOCT2 cells. Pharmacokinetics of cisplatin was investigated in male and female rats because the renal expression level of rOCT2 was higher in male than female rats. The renal uptake clearance of cisplatin was greater in male than female rats, while the hepatic uptake clearance was similar between the sexes. In addition, glomerular filtration rate and liver function were unchanged, but N-acetyl-β- d-glucosaminidase activity in the bladder urine and the urine volume were markedly increased 2 days after the administration of 2 mg/kg of cisplatin in male rats. Moreover, cisplatin did not induce the elevation of urinary N-acetyl-β- d-glucosaminidase activity in the castrated male rats whose renal rOCT2 level was lower than that of the sham-operated rats. In conclusion, the present results indicated that renal rOCT2 expression was the major determinant of cisplatin-induced tubular toxicity.