King Oyster Mushroom, Pleurotus eryngii (Agaricomycetes), Extract Can Attenuate Doxorubicin-Induced Lung Damage by Inhibiting Oxidative Stress in Rats.

Doxorubicin (DOX), a broad spectrum chemotherapeutic, has toxic effects on healthy tissues. Mitochondrial processes and oxidative stress act in the DOX-induced toxicity, therefore antioxidant therapies are widely used. The study was aimed to evaluate the therapeutic potential of Pleurotus eryngii extract (PEE), an extract of a fungus with antioxidant properties, against DOX-induced lung damage. Rats were divided into Control, DOX, DOX + PEE, and PEE groups (n = 6). DOX was administered intraperitoneally in a single dose (10 mg/kg BW) and PE (200 mg/kg BW) was administered by oral gavage every other day for 21 days. Histopathological evaluations, immunohistochemical analyses, total oxidant status (TOS)/total antioxidant status (TAS) method, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. DOX led to severe histopathological disruptions in rat lungs. Also, DOX remarkably increased the expression of dynamin 1 like (DRP1) and decreased the expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) genes, which are related to mitochondrial dynamics. Moreover, DOX caused an increase in TOS/ TAS and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. On the other hand, PEE treatment remarkably normalized the histopathological findings, mitochondrial dynamics-related gene expressions, markers of oxidative stress, and DNA damage. The present study signs out that PEE can ameliorate the DOX-mediated lung toxicity and the antioxidant mechanism associated with mitochondrial dynamics can have a role in this potent therapeutic effect.

The therapeutic effect of hesperetin on doxorubicin-induced testicular toxicity: Potential roles of the mechanistic target of rapamycin kinase (mTOR) and dynamin-related protein 1 (DRP1).

Clinical utilization of doxorubicin (DOX), which is a commonly used chemotherapeutic, is restricted due to toxic effects on various tissues. Using hesperetin (HST), an antioxidant used in Chinese traditional medicine protects testis against DOX-induced toxicity although the molecular mechanisms are not well-known. The study was aimed to examine the possible role of the mechanistic target of rapamycin kinase (mTOR) and dynamin 1-like dynamin-related protein 1 (DRP1) in the therapeutic effects of HST on the DOX-induced testicular toxicity. Rats were divided into Control, DOX, DOX + HST, and HST groups (n = 7). Single-dose DOX (15 mg/kg) was administered intraperitoneally and HST (50 mg/kg) was administered by oral gavage every other day for 28 days. Total antioxidant status (TAS), histopathological evaluations, immunohistochemistry, and gene expression level detection analyses were performed. Histopathologically, DOX-induced testicular damage was ameliorated by HST treatment. DOX reduced testicular TAS levels and increased oxidative stress markers, 8-Hydroxy-deoxyguanosine (8-OHdG), and 4-Hydroxynonenal (4-HNE). Also, upregulated mTOR and DRP1 expressions with DOX exposure were decreased after HST treatment in the testis (p < 0.05). On the other hand, DOX-administration downregulated miR-150-5p and miR-181b-2-3p miRNAs, targeting mTOR and mRNA levels of beclin 1 (BECN1) and autophagy-related 5 (ATG5), autophagic markers. Furthermore, these levels were nearly similar to control testis samples in the DOX + HST group (p < 0.05). The study demonstrated that HST may have a therapeutic effect on DOX-induced testicular toxicity by removing reactive oxygen species (ROS) and by modulating the mTOR and DRP1 expressions, which have a critical role in regulating the balance of generation/elimination of ROS.

The investigation of effect of alpha lipoic acid against damage on neonatal rat lung to maternal tobacco smoke exposure.

This study was carried out to determine the changes in the lungs of the rat pups exposed to tobacco smoke during pregnancy period and to investigate the protective effects of alpha lipoic acid, which is administered during pregnancy, on these changes. Spraque-Dawley female rats were divided into four groups: control, tobacco smoke (TS), tobacco smoke + alpha lipoic acid (TS + ALA) and alpha lipoic acid (ALA). The rats in control group were untreated. Rats were exposed to TS twice a day for one hour starting from eight weeks before mating and during pregnancy. 20 mg / kg of ALA was administered to rats. On 7th and 21st days 7 of the pups from each group were decapitated. Histological, morphometric, biochemical and quantitative real-time RT-PCR analyzes were performed. Histopathological and biochemical changes were observed in TS group. While a significant decrease was observed both in SP-A and VEGF immunoreactivities and mRNA levels, caspase-3 immunoreactivity and TUNEL positive cells were increased in TS group. It is suggested that prenatal TS exposure leads to morphological and histopathological changes on lung development by causing oxidative damage in lungs of neonatal rats and the maternal use of ALA can provide a limited protective effect on the neonatal lung development against this oxidative stress originating from TS. Although pregnant women are increasingly aware on health risks of smoking, environmental tobacco smoke exposure is still a widespread problem. For this reason, it is thought that this damage can be partially reduced by some antioxidant supplements in pregnancy.