Protective effect of myricetin, apigenin, and hesperidin pretreatments on cyclophosphamide-induced immunosuppression.

Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats.Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide + myricetin (100 mg/kg), cyclophosphamide + myricetin (200 mg/kg), cyclophosphamide + apigenin (100 mg/kg), cyclophosphamide + apigenin (200 mg/kg), cyclophosphamide + hesperidin (100 mg/kg), and cyclophosphamide + hesperidin (200 mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14 d, while cyclophosphamide application (200 mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups.Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow.Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.

Protective Role of Myricetin and Fisetin Against Nephrotoxicity Caused by Lead Acetate Exposure through Up-regulation of Nrf2/HO-1 Signalling Pathway.

The effect of various flavonoids against oxidative stress and inflammation caused by lead exposure has been investigated. However, the protective effects of myricetin (MYC) and fisetin (FST), which are known to have potent antioxidant properties, against nephrotoxicity caused by exposure to lead acetate (LA), the water-soluble form of lead, have not been investigated. Our study investigated the protective role of these flavonoids against LA intoxication-induced nephrotoxicity. In our study, 42 male rats were used. The rats were randomly selected and divided into 6 groups. These groups were: control, LA (100 g/kg), LA + MYC (100 mg/kg), LA + MYC (200 mg/kg), LA + FST (100 mg/kg) and LA + FST (200 mg/kg). All chemicals were administered daily by gavage for 28 days. According to the experimental protocol, the animals were sacrificed and their kidney tissues were isolated. Serum biochemical parameters, histological examinations, levels of several trace elements, oxidative stress and inflammatory parameters at both biochemical and molecular levels in kidney tissues were examined. After LA administration, tissue lead levels increased and zinc levels decreased. This situation was reversed by MYC and FST treatment. Oxidative stress and inflammatory response were increased in the kidney tissue of LA-treated rats and renal function was impaired. It was observed that both doses of MYC and high dose of FST could prevent nephrotoxicity. Oral administration of both doses of MYC and high dose FST ameliorated the changes in biochemical, oxidative and inflammatory parameters. Restoration of normal renal tissue architecture was also demonstrated by histological studies. MYC and FST were found to have promising biological activity against LA-induced nephrotoxicity, acting by attenuating inflammation and oxidative stress and improving antioxidant status.