Objectives: Distant liver injury is a complication of renal ischemia-reperfusion (I/R) injury, which imposes mortality and economic burden. This study aimed to elucidate the cross-talk of endoplasmic reticulum (ER) stress and mitochondrial perturbations in renal I/R-induced liver injury, and the potential hepatoprotective effect of azilsartan (AZL).Methods: Male albino Wister rats were pre-treated with AZL (3 mg/kg/day, PO) for 7 days then a bilateral renal I/R or sham procedure was performed. Activities of liver enzymes were assessed in plasma. The structure and ultra-structure of hepatocytes were assessed by light and electron microscopy. Markers of ER stress, mitochondrial biogenesis and apoptosis were analyzed in livers of rats.Results: Renal ischemic rats showed higher plasma levels of liver enzymes than sham-operated rats, coupled with histological and ultra-structural alterations in hepatocytes. Mechanistically, there was up-regulation of ER stress markers and suppression of mitochondrial biogenesis-related proteins and enhanced apoptosis in livers of renal ischemic rats. These abnormalities were almost abrogated by AZL pretreatment.Discussion: Our findings uncovered the involvement of mitochondrial perturbations, ER stress and apoptosis in liver injury following renal I/R, and suggested AZL as a preconditioning strategy to ameliorate remote liver injury in patients susceptible to renal I/R after adequate clinical testing.

There are no curative treatments for Parkinson's disease (PD), and current treatments focus on symptomatic management. This study aimed to investigate the beneficial effects of combining L-DOPA/Carbidopa with essential cofactors (vitamin (VIT) B complex and coenzyme Q10 (CoQ10)), alone or in conjunction with vinpocetine (VIN) or cocoa, as a potential strategy to enhance neuroprotection in rotenone (RT)-induced PD rat model, highlighting mechanistic insights into their underlying neuroprotective mechanisms and focusing on addressing oxidative stress, inflammation, autophagy, and apoptosis. These combinations were tested on adult male Wistar rats allocated into six groups. Group I received saline (normal control), while groups II-VI were injected with RT for 19 days to induce PD. Group II received RT alone, group III received daily oral L-DOPA/Carbidopa, and groups IV-VI received L-DOPA/Carbidopa with VIT B complex and CoQ10, either alone (Group IV) or combined with cocoa (Group V) or VIN (Group VI). These treatments markedly improved RT-induced perturbations in locomotor and cognitive outcomes; neurotransmitters' levels; oxidative stress (Nrf2/HO-1, MDA, INOS, SOD and TAC); inflammatory (NF-κB, TNF-α, IL-1β, GFAP and COX-2); neurotrophic (AKT/CREB/BDNF); apoptotic (BAX, caspase-3, AIF, and Bcl-2); and autophagic (AMPK/SIRT-1/Beclin-1) biomarkers; histopathological findings and tyrosine hydroxylase (TH) immunoexpression. Furthermore, the best outcomes were observed in cocoa and VIN combinations. These results indicated that combining L-DOPA with CoQ10 and VIT B complex in conjunction with either VIN or cocoa could provide a potential strategy for managing motor impairments and preventing neurodegeneration in PD. The interaction between key signaling pathways, including Nrf2/HO-1, NF-kB, AMPK/SIRT-1, and AKT/GSK-3β/CREB/BDNF, likely mediates this effect. However, further clinical validation is required to assess this approach's real-world applicability and therapeutic potential.

Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF.