Possible mitigating effect of adropin on lung injury in diabetic rats: Targeting the role of Rho A/Rho-associated kinase pathway.

This study evaluated possible mitigating effect of adropin on lung injury in diabetic rats, targeting role of Rho A/Rho-associated kinase pathway. Rats were allocated into four groups: control, adropin, diabetic, and diabetic+adropin groups. At the termination of the experiment, serum fasting glucose, insulin and adropin levels and insulin resistance were calculated. Wet/dry ratio, histopathological, immunohistochemical analyses, and relative real time gene expression of lung tissue was determined. Interleukin-6, tumor necrosis factor alpha, malondialdehyde, 8-Oxo-2'-deoxyguanosine, reduced glutathione, superoxide dismutase, Bcl-2, BAX, myeloperoxidase, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and transforming growth factor-ß were determined in lung tissue. Adropin treatment in diabetic rats notably attenuated hyperglycemia and insulin resistance. Also, it mitigated diabetic lung injury via suppressing effect on Rho A/ROCK pathway, apoptosis, inflammatory reactions, oxidative stress, and fibrosis of lung tissue. Adropin can be considered as a promising therapeutic agent for treating diabetic lung injury.

Possible protective effects of CO Q10 against vincristine-induced peripheral neuropathy: Targeting oxidative stress, inflammation, and sarmoptosis.

Vincristine is a chemotherapy drug that belongs to the vinca alkaloids group. It is used for treatment of hematologic malignancies and several solid tumors. Vincristine-induced peripheral neuropathy is a major dose-limiting side effect. Coenzyme Q10 (Co Q10), an essential component of the mitochondrial electron transport chain, participates in energy production. It is a powerful fat-soluble antioxidant and also exerts anti-inflammatory effects. Therefore, this study was aimed to focus on the mechanistic insights of vincristine-induced peripheral neuropathy in addition to shedding the light on the modulatory effect of Co Q10. Twenty-eight rats were randomly divided into four groups. Peripheral neuropathy was induced by intraperitoneal injection of vincristine (0.1 mg/kg body weight). Co Q10 was injected intraperitoneally (10 mg/kg body weight) for 24 days. Sciatic nerve MDA, TAC, GSH, 8-OHdG, TNF-α, IL-1ß, and NF-κB levels were assessed. Gene expression of SARM1 and Nrf2 was also assessed. Serum neurofilament light chain was immunoassayed, in addition to the behavioral assessment. Co Q10 significantly improved oxidative stress and inflammatory biomarkers. It also decreased serum NFL levels. It enhanced Nrf2 and decreased SARM1 gene expression. Histopathological findings proved the biochemical and molecular findings. Our results support Co Q10 as a potential protective agent against vincristine-induced peripheral neuropathy.

Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: Targeting implication of endoplasmic reticulum stress.

This study investigated the potential effect of adrenomedullin (ADM) on metabolic and endocrinal dysfunctions in experimentally induced polycystic ovary. Twenty-four female Wistar rats were allocated into three groups: control; polycystic ovary syndrome (PCOS) in which PCOS was induced by letrozole, orally in a dose of 1 mg/kg once daily for 3 weeks; and ADM group in which ADM was injected intraperitonally in a dose of 3.5/µg/twice daily for 4 weeks. At the end of the experimental period, the serum sex hormone profile, ADM, fasting glucose, insulin, homeostatic model assessment of insulin resistance, and lipid parameters were determined. Ovarian tissue homogenates were used to determine malondialdehyde, total antioxidant capacity, glutathione peroxidase activity, tumor necrosis factor α, interleukin 6, B cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein. The profibrotic growth factors, including transforming growth factor ß1 and connective tissue growth factor, were determined; and also, the relative gene expression of endoplasmic reticulum (ER) stress, including (Xbox-binding protein-1 [XBP-1], activating transcription factor 6 [ATF6], and homologous protein [CHOP]), serine/threonine kinase 1 (Akt1), phosphatidylinositol 3-kinase (PI3K), and peroxisome proliferator-activated receptor γ (PPAR-γ) were determined. Finally, histopathological analysis of the ovaries was evaluated. PCOS group exhibited increased ER stress, suppressing of PI3K/Akt1 and PPAR-γ pathways, imbalance of sex hormonal profile, hyperglycemia, insulin resistance, dyslipidemia, increased profibrotic factors, and abnormal ovarian histopathological picture, while ADM treatment alleviated these disturbances occurring in the PCOS model. We concluded that ADM mitigated PCOS via attenuating the ER stress, in addition to activation of PI3K/Akt1 and PPAR-γ pathways, its antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic properties.