Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide-induced biochemical toxicity.

Walnut (Juglans regia L.) is extensively used in traditional systems of medicine for treatment of various ailments. It is described as an anticancer, tonic, blood purifier and detoxifier agent. The present study was undertaken to investigate modulatory effects of walnut extract on the toxicity of an anticancer drug, cyclophosphamide (CP) with special reference to protection against disruption of drug metabolizing and antioxidant enzymes. Plant extract+CP group animals showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione S-transferase (GST), glutathione peroxidase (GP) and catalase (CAT) in both liver and kidneys. But plant extract restored the activity of superoxide dismutase (SOD) and the level of reduced glutathione (GSH) in the kidneys only when compared with CP-treated animals. Plant extract treatment alone caused significant reduction in the content of CYP in the kidneys mainly. The extract showed a significant increase in the level of GSH and in the activities of GP in both the tissues and CAT in liver only, whereas no significant change was observed in the activities of GST and SOD. CP treatment resulted in a significant (P < 0.01) increase in the lipid peroxidation (LPO) in the liver and kidneys compared with controls, while the extract+CP treated group showed a significant decrease in the LPO in liver and kidneys when compared with the CP-treated group. The study shows that the use of J. regia extract might be helpful in abrogation of CP toxicity during the chemotherapy.

Effect of endosulfan on antioxidants of freshwater fish Channa punctatus Bloch: 1. Protection against lipid peroxidation in liver by copper preexposure.

Effect of a single exposure of endosulfan (5 ppb) on catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and reduced glutathione (GSH) of liver, kidney, and gill of a freshwater fish (Channa punctatus Bloch) were evaluated after 24 h of treatment. Endosulfan exposure resulted in a significant induction (p < 0.05-0.001) of GPx, GST activity, and GSH levels in all the organs. However, CAT activity was found to be significantly decreased (p < 0.01-0.001). Lipid peroxidation (LPO) values were also determined in liver, kidney, and gill and a significant increase in LPO values (p < 0.05-0.01) was observed in all the organs. We also investigated whether preexposure to low concentration of copper (10 ppb) for 4 weeks has any protective effect against endosulfan-induced oxidative damage. In copper-acclimatized endosulfan-exposed fish, a significant decrease in GPx (p < 0.001), GST (p < 0.05), GSH (p < 0.001) levels, and LPO (p < 0.01) was observed in the liver, whereas CAT activity was increased significantly (p < 0.001). However, kidney and gill did not show any significant alterations in antioxidant levels. The results of this study demonstrate that endosulfan induces peroxidative damage in liver, kidney, and gill in response to which levels of antioxidant were modulated. However, when fish preacclimatized to copper were exposed to endosulfan, protection against oxidative damage was observed only in the liver. It is proposed that measurement of antioxidants in fish tissues may prove to be useful in biomonitoring of exposure to aquatic pollutants.

Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice.

Cassia occidentalis L. (Kasaundi) is a widely used medicinal plant. Earlier, we have shown that it possesses antimutagenic activity against benzo[a]pyrene (BaP) and cyclophosphamide (CP)-induced mutagenicity in mice. In this study, we investigated if this plant could also provide protection against CP-induced immunosuppression in animal models. Swiss albino male mice were treated per os with the aqueous extract of C. occidentalis (100 mg/kg, body weight (b.w.)) for 14 days. Cyclophosphamide was given intraperitoneally in a single dose of 50 mg/kg b.w. Body weight, relative organ weight, lymphoid organ cellularity, hemagglutination titre (HT), plaque forming cell (PFC) assay and quantitative hemolysis of SRBC (QHS) were studied in these animals. CP, as expected, showed suppressive effects on lymphoid organ weight and cellularity and other parameters of humoral immunity. Plant extract treatment itself produced no toxicity. The administration of plant extract to CP-exposed animals resulted in improved humoral responses. C. occidentalis treatment significantly (P<0.01) enhanced PFC response in CP-treated animals. In QHS assay, also C. occidentalis showed protection in CP-treated animals. Bone marrow cell counts, which were reduced in CP-treated animals, were reversed significantly (p<0.01) to normal levels in CP+ plant extract group animals. In our earlier study, we found that C. occidentalis modulated hepatic drug metabolizing enzymes. It is suggested that by a similar mechanism, it may be influencing the hematotoxic and immunotoxic responses of cyclophosphamide.

Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice.

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen.