The anticancer drug cyclophosphamide (CP) has nephrotoxic effects besides its urotoxicity, which both in turn limit its clinical utility. The nephrotoxicity of CP is less common compared to its urotoxicity, and not much importance has been given for the study of mechanism of CP-induced nephrotoxicity so far. Overproduction of reactive oxygen species (ROS) during inflammation is one of the reasons of the kidney injury. Selenoproteins play crucial roles in regulating ROS and redox status in nearly all tissues; therefore, in this study, the nephrotoxicity of CP and the possible protective effects of seleno L-methionine (SLM) on rat kidneys were investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats each. The control group received saline, and other rats were injected with CP (100 mg/kg), SLM (0.5 or 1 mg/kg), or CP+ SLM intraperitoneally. Malondialdehyde (MDA) and glutathione (GSH) levels in kidney homogenates of rats were measured, and kidney tissues were examined under the microscope. CP-treated rats showed a depletion of renal GSH levels (28% of control), while CP+SLM-injected rats had GSH values close to the control group. MDA levels increased 36% of control following CP administration, which were significantly decreased after SLM treatment. Furthermore, these biochemical results were supported by microscopical observations. In conclusion, the present study not only points to the therapeutic potential of SLM in CP-induced kidney toxicity but also indicates a significant role for ROS and their relation to kidney dysfunction.

The objective of this study is to evaluate the possible protective effects of selenium (Se) against cyclophosphamide (CP)-induced acute cardiotoxicity in rats. A total of 42 male Spraque-Dawley rats were divided into six groups (n = 7). Rats in the first group were served as control. Rats in the second group received CP (150 mg/kg) at the sixth day of experiment. Animals in the third and fourth groups were treated with only 0.5 and 1 mg/kg Se respectively for six consecutive days. Rats in the fifth and sixth groups received respective Se doses (0.5 or 1 mg/kg) for 6 days and then a single dose of CP administered on the sixth day. On day 7, the animals were sacrificed; blood samples were collected to measure malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and ischemia-modified albumin (IMA) levels. Heart tissues were processed routinely and tissue sections were stained with H + E for light microscopic examination. In the CP-treated rats MDA, LDH, CK-MB, and IMA serum levels increased, while GSH levels decreased. Microscopic evaluation showed that tissue damage was conspicuously lower in CP plus Se groups. Moreover, 1 mg/kg Se was more protective than 0.5 mg/kg Se as indicated by histopathological and biochemical values. In conclusion, Se is suggested to be a potential candidate to ameliorate CP-induced cardiotoxicity which may be related to its antioxidant activity.

Cyclophosphamide (CP) is an antineoplastic drug that induces kidney damage via producing oxidative stress. Carvacrol (CAR) has antioxidative effect and we postulated that it can be protective against CP-induced nephrotoxicity. Six groups (n = 7) of rats (control, 100 mg/kg CP, CP+5 mg/kg CAR, CP+10 mg/kg CAR, 5 mg/kg CAR, and 10 mg/kg CAR) were injected intraperitoneally. Serum malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), creatinine (CRE), total antioxidant capacity (TAC), and total oxidant state (TOS) were measured, and oxidative stress indexes (OSI) were calculated. Kidneys were also analyzed histologically. In CP-alone group MDA, CRE, TOS, and OSI levels increased whereas GSH, SOD, CAT, and TAC levels decreased compared with control group. In CP plus CAR groups, MDA, TOS, and OSI levels decreased whereas GSH, SOD, CAT, and TAC levels increased compared with CP-alone group. However, CRE levels were similar in CP-alone and CP+5 CAR group whereas decreased in CP+10 CAR group. CP+10 CAR group was significantly different in all parameters (except TAC) from CP+5 CAR group. Kidney microscopy was showed lower tissue damage in CP plus CAR groups. In conclusion, 10 mg/kg CAR is more effective than 5 mg/kg CAR in prevention of CP-induced oxidative damage on kidney.

Cyclophosphamide (CP) is a common anticancer drug, but its use in cancer treatment is limited due to its severe toxicities induced mainly by oxidative stress in normal cells. Reactive oxygen species (ROS) lead to multiple organ injuries, including the kidneys. Selenium (Se) is a nutritionally essential trace element with antioxidant properties. In the present study, the possible protective effect of Se on CP-induced acute nephrotoxicity was investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats in each. The control group received saline, and other groups were injected with CP (150 mg/kg), Se (0.5 or 1 mg/kg), or CP + Se intraperitoneally. Total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI), creatinine, and cystatin C (Cys C) levels were measured in the sera. In addition, kidney tissues were examined histologically. In the CP alone treated rats, creatinine, Cys C, TOS, and OSI levels increased, while TAC level decreased. CP-induced histological damages were decreased by co-treatment of Se and biochemical results supported the microscopic observations. In conclusion, our study points to the therapeutic potential of Se and indicates a significant role of ROS in CP-induced kidney toxicity.

Cyclophosphamide (CP) is a widely used antineoplastic drug that causes toxicity in the normal cell due to its metabolites. The major drawback of this drug is an undesirable myelosuppression. Selenium (Se) is a potent nutritional antioxidant that carries out biological effects by its incorporation into selenoproteins, such as glutathione peroxidase (GPx). The possible protective effects of seleno-L-methionine (SLM) against CP-related toxicity of blood cells and bone marrow of rats were investigated in this study. Intraperitoneal (i.p) administration of 50, 100, or 150 mg/kg of CP caused, in a dose-dependent manner, reductions in the number of leukocytes (78, 89, and 92%, respectively), thrombocytes (22, 33, and 52%, respectively), and bone marrow-nucleated cells (72, 90, and 94%, respectively). The groups that had CP treatment alone were killed 3 days after the CP injection. For the groups having CP+SLM, SLM (0.4 or 0.8 mg/kg i.p) administration was started 3 days earlier than the CP administration and continued to the end of the experiment (6 days). On day 4, the animals were weighed again, relative doses of CP were estimated, and CP+SLM was administered together. On day 7, blood samples were collected and bone marrow of animals were resected under anesthesia. The results indicated that treatment of rats within a select dose range of SLM could reduce CP-induced toxicity on blood cells and bone marrow.