Cyclophosphamide (CP) is a common chemotherapeutic agent that is effective against a wide variety of tumors. The associated hepatotoxicity and nephrotoxicity, however, limit its therapeutic use. Naringin (NG) is a natural flavanone glycoside that has pharmacological and therapeutic activities, such as anti-inflammation, anti-apoptotic, and antioxidant properties. Therefore, the present study was undertaken to evaluate the protective effect of NG against CP-induced hepatotoxicity and nephrotoxicity in rats. Rats were pre-treated with NG (50 and 100 mg/kg b.w.) for 7 days before administering a single dose of CP (200 mg/kg b.w.) on the seventh day. CP-induced hepatotoxicity and nephrotoxicity were associated with an increase in serum toxicity markers and a decrease in antioxidant enzyme activities. CP also induced inflammatory responses by increasing the levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it activated the apoptotic and autophagic pathway by increasing cysteine aspartate-specific protease-3 (caspase-3) expression and light chain 3B (LC3B) level and also increased the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is the marker of oxidative DNA damage. Pre-treatment with NG (50 and 100 mg/kg), however, significantly decreased serum toxicity markers, increased antioxidant enzyme activities, and regulated inflammation, apoptosis, autophagy, and oxidative DNA damage in hepatic and renal tissues. These results indicated that NG was an effective protectant against CP-induced hepatotoxicity and nephrotoxicity.

Doxorubicin (DXR) is a highly effective drug for chemotherapy. However, cardiotoxicity reduces its clinical utility in humans. The present study aimed to assess the ameliorative effect of curcumin against DXR-induced cardiotoxicity in rats. Rats were subjected to oral treatment of curcumin (100 and 200 mg/kg body weight) for 7 days. Cardiotoxicity was induced by single intraperitoneal injection of DXR (40 mg/kg body weight) on the 5th day and the rats sacrificed on 8th day. Curcumin ameliorated DXR-induced lipid peroxidation, glutathione depletion, decrease in antioxidant (superoxide dismutase, catalase, and glutathione peroxidase) enzyme activities, and cardiac toxicity markers (CK-MB, LDH, and cTn-I). Curcumin also attenuated activities of Caspase-3, cyclooxygenase-2, inducible nitric oxide synthase, and levels of nuclear factor kappa-B, tumor necrosis factor-α, and interleukin-1β, and cardiac tissue damages that were induced by DXR. Moreover, curcumin decreased the expression of 8-OHdG and 3,3'-dityrosine. This study demonstrated that curcumin has a multi-cardioprotective effect due to its antioxidant, anti-inflammatory, and antiapoptotic properties.

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Cisplatin (CP) treatment causes damage in the male reproductive system. Rutin (RUT) is a naturally occurring flavonoid glycoside that has antioxidant and anti-inflammatory properties. This study aimed to investigate effects of RUT against cisplatin-induced reproductive toxicity in male rats. Twenty-one adult male Sprague Dawley rats were used. The control group received physiological saline with oral gavage during 14 days, and physiological saline was injected intraperitoneally (IP) in 10th days of study. CP Group received physiological saline during 14 days, and 10 mg kg CP was injected IP in 10th day. RUT + CP group received RUT (150 mg kg ) during 14 days, and 10 mg kg CP was injected IP in 10th day. Spermatological parameters (including motility, cauda epididymal sperm density, dead sperm percentage and morphological sperm abnormalities), biochemical (MDA, GSH, GSH-px, SOD and CAT), histological (H&E dye) and immunochemistry evaluations of testicles were evaluated. CP treatment caused damage on some spermatological parameters, increased the oxidative stress and induced testicular degeneration and apoptosis when compared to the control group. However, RUT treatment mitigates these side effects when compared to the CP alone group. IT is concluded that RUT treatment may reduce CP-induced reproductive toxicity as a potential antioxidant compound.

Silymarin (SLY) and naringin (NRG) are natural flavonoids that have been reported to have many benefits and medicinal properties. The present study was designed to investigate the protective effect of SLY and NRG against methotrexate (MTX)‐induced nephrotoxicity in experimental animals. Rats were subjected to oral pretreatment of SLY (25 and 50 mg/kg body weight (b.w.)/day) and NRG (50 and 100 mg/kg b.w./day) for 7 days against renal toxicity induced by single intraperitoneal administration of MTX (20 mg/kg b.w.). MTX resulted in an increase in serum toxicity markers, lipid peroxidation, and reduction in activities of antioxidant enzymes. Additionally, MTX provoked inflammatory responses by increasing the levels of TNF‐α, IL‐1β, IL‐6, NF‐κB, and activation of COX‐2 and iNOS. Furthermore, MTX administration caused apoptosis and autophagy by increasing activity of Caspase‐3 and light chain 3B level. Conversely, SLY and NRG therapy significantly decreased these values in rats. This study demonstrated that SLY and NRG protect against MTX‐induced nephrotoxicity. Practical applications Chemotherapeutic drugs have been used for cancer treatment for many years. However, in the treatment process, they may damage organs such as liver and kidney, prolong the treatment process and negatively affects patient welfare. This study revealed that silymarin and naringin exhibited potent anti‐inflammatory, antiapoptotic, and antiautophagic effect in renal injury caused by methotrexate, a chemotherapeutic drug. Therefore, treatment silymarin and naringin can be used for the beneficial effect against methotrexate‐induced kidney damage in cancer chemotherapy.