Doxorubicin (DOX) is a well-known chemotherapeutic drug for most malgnencies including breast cancer and leukemia whilst the usage of DOX is limited owing to its cardiotoxicity. The present study analyzed the effects of crocin on doxorubicin's cardiotoxic efect in rat myocardium and searched their mechanistic interaction in the pathogenesis of DOX-induced myocardial toxicity. Forty rats were divided into four groups; (a) control (received normal saline as a dose of 1 ml/kg by ip for 15 days), (b) Crocin (received crocin as a dose of 40 mg/kg/24h by ip for 15 days), (c) DOX (received DOX as a dose of 2 mg/kg/48h by ip in six injection, cumulative dose 12 mg/kg), and (d) DOX + Crocin (received DOX as a dose of 2 mg/kg/48h by ip in six injection and crocin as a dose of 40 mg/kg/24h ip for 15 days). According to the present study, DOX administration caused signi cant increases in lipid indices (triglyseride, low-dencity lipoproteins and very low-dencity lipoproteins) as well as cardiac markers (Creatine kinase-muscle/brain and Cardiac Troponin I). Morever, DOX caused signi cant increases in oxidative stress parameters (malondialdehyde and total oxidant status) as well as decreases in antioxidant defense systems (glutathione, superoxide dismutase, catalase and total antioxidant status). The present study also demonstrated that co-administration of crocin with DOX signi cantly ameliorated the lipid pro le and biochemical parameters in rats receiving DOX. The results were supported by histopathological and immunohistochemical evaluations. Taken together, our results reveal that crocin might be a cardioprotective agent in DOX treated patients for cancer.

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Gout is an in ammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent in ammation inducers. Melatonin (MLT) is a powerful endogenous anti-in ammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-in ammatory and anti-oxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (On the 30th day, single dose 20 mg/ml, intraperitoneal), MSU+MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU+PINX and MSU+PINX+MLT. PNX procedure was performed on the rst day of the study. As compared to the controls, the results showed that MSU administration caused signi cant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, signi cant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status were observed. A statistically signi cant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were signi cantly reduced in the MSU+MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of in ammation, were signi cantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proin ammatory cytokine production.

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