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The goal of the current study was to examine the therapeutic potential of green coffee bean extract (GCBE) in the treatment of diabetic hepatic damage induced by high-fat diet (HFD) and streptozotocin (STZ) administration. The novelty of this study lies in constructing a newly stabilized in vivo obese diabetic animal model in rats using HFD/STZ for investigating the dose-dependent effect of two commonly used doses of GCBE in hepatoprotection against oxidative stress-induced hepatic damage by measuring many parameters that have not been carried out previously in other studies. GCBE that was used in this study was a hot water extract of green coffee beans with a concentration of 0.1 g ml−1. Male albino rats were given a single dose of STZ (35 mg kg−1), and HFD to induce diabetes mellitus (DM). For 28 days, two separate doses of GCBE 50 mg kg−1 and 100 mg kg−1 were administered orally to diabetic animals. Leptin, liver enzymes, oxidative stress parameters, inflammatory parameters, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and lipid profile levels were examined. Real-time PCR and ELISA were used to quantitatively detect the mRNAs of the genes involved in the insulin signaling pathway, the genes involved in glucose metabolism, and the amounts of proteins. The levels of FPG, lipid profile, liver enzymes, inflammatory markers, and leptin in the HFD/STZ diabetic group revealed a considerable spike, while they considerably decreased after GCBE treatment in a dose-dependent manner. After GCBE treatment, the diabetic group showed a significant rise in the antioxidant markers glutathione, superoxide dismutase, and catalase, as well as a decrease in malondialdehyde and nitric oxide levels. The liver changes caused by HFD/STZ were entirely reversed by GCBE, and most intriguingly, in a dose-dependent manner. We concluded that GCBE can repair the hepatic oxidative damage caused by HFD and STZ by reversing all the previously measured parameters and improving the insulin signaling pathways. GCBE demonstrated strong antifree radical activity and significantly protected cells from oxidative damage caused by HFD/STZ.

Ferritinophagy is one of the most recent molecular mechanisms affecting cardiac function. In addition, it is one of the pathways by which doxorubicin, one of the anticancer drugs commonly used, negatively impacts the cardiac muscle, leading to cardiac function impairment. This side effect limits the use of doxorubicin. Iron chelators play an important role in hindering ferritinophagy. Antioxidants can also impact ferritinophagy by improving oxidative stress. In this study, it was assumed that the antioxidant function of melatonin could promote the action of deferoxamine, an iron chelator, at the level of ferritinophagy. A total of 42 male Wistar rats (150–200 g) were divided into seven groups (n = 6) which consisted of group I: control normal, group II: doxorubicin (Dox), group III: melatonin (Mel), group IV: deferoxamine (Des), group V: Mel + Dox, group VI: Des + Dox, and group VII: Mel + Des + Dox. Groups III, V and VII were orally pretreated with melatonin 20 mg/kg/day for 7 days. Groups IV, VI and VII were treated with deferoxamine at a 250 mg/kg/dose once on D4 before Dox was given. Doxorubicin was given at a 20 mg/kg ip single dose. On the 8th day, the rats were lightly anaesthetized for electrocardiography analysis and echocardiography. Serum samples were collected and then sacrificed for tissue sampling. The following biochemical assessments were carried out: PCR of NCOA4, IREB2, FTH1, SLC7A11, and GPX4; and ELISA for serum cTnI, serum transferrin, tissue GSH, and malondialdehyde. In addition, histopathological assessment of heart injury; immunostaining of caspase-3, Bax, and Bcl2; and physiological function assessment by ECG and ECHO were carried out. Doxorubicin-induced acute significant cardiac injury with increased ferritinophagy and apoptosis responded to single and combined prophylactic treatment, in which the combined treatment showed mostly the best results. In conclusion, using melatonin as an antioxidant with an iron chelator, deferoxamine, could hinder the hazardous cardiotoxic effect of doxorubicin. However, further studies are needed to detect the impact of higher doses of melatonin and deferoxamine with a prolonged treatment period.