Purpose: Globally, sepsis, which is a major health issue resulting from severe infection-induced inflammation, is the fifth biggest cause of death. This research aimed to evaluate, for the first time, the molecular effects of gabapentin's possible nephroprotective potential on septic rats by cecal ligation and puncture (CLP). Methods: Sepsis was produced by CLP in male Wistar rats. Evaluations of histopathology and renal function were conducted. MDA, SOD, GSH, TNF-α, IL-1β, and IL-6 levels were measured. qRT-PCR was utilized to determine the expression of Bax, Bcl-2, and NF-kB genes. The expression of Nrf-2 and HO-1 proteins was examined by western blotting. Results: CLP caused acute renal damage, elevated the blood levels of creatinine, BUN, TNF-α, IL-1β, and IL-6, reduced the expression of Nrf-2 and HO-1 proteins and the Bcl-2 gene expression, and upregulated NF-kB and Bax genes. Nevertheless, gabapentin dramatically diminished the degree of the biochemical, molecular, and histopathological alterations generated by CLP. Gabapentin reduced the levels of proinflammatory mediators and MDA, improved renal content of GSH and SOD, raised the expression of Nrf-2 and HO-1 proteins and Bcl-2 gene, and reduced the renal expression of NF-kB and Bax genes. Conclusion: Gabapentin mitigated the CLP-induced sepsis-related acute kidney injury through up-regulating Nrf-2/HO-1 pathway, repressing apoptosis, and attenuating the oxidative stress status by reducing the levels of the proinflammatory mediators and enhancing the antioxidant status.

Vitis viniferaedible leaf extract loaded on a Carbopol gel was prepared to maximize the wound healing and anti-MRSA properties. The extract's mode of action has been comprehensively investigated byin vitro,in vivo, andin silicoexperiments.

This study aimed to assess the preventive potential of apremilast (APRE) against methotrexate (MTX)-induced renal damage in rats through modulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling and toll-like receptor 4/nuclear factor-kappa B/p38 mitogen-activated protein kinase/caspase-3 (TLR4/NF-κB/p38 MAPK/Caspase-3) signaling pathways. Four groups of male Wistar albino rats were assigned: control, APRE, MTX, MTX + APRE. Histopathological investigation and biochemical analysis of the serum renal damage indicators (urea and creatinine) were used to evaluate the renal toxicity of MTX. Testing for renal malondialdehyde (MDA) and reduced glutathione (GSH) was conducted. The levels of renal tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), Nrf2, HO-1, and cleaved caspase-3 were measured using the ELISA method. Using an immunohistochemistry method, the expression of NF-κB p65 in the kidney was investigated. Western blotting was used to examine the expression of TLR4 and p38 MAPK proteins. MTX administration resulted in significant renal injury, as evidenced by elevated serum urea and creatinine levels. The kidneys were significantly affected as evidenced by histopathological alterations and increased levels of renal MDA, TNF-α, IL-6, Bcl-2-associated x (Bax), and cleaved caspase-3, alongside decreased levels of GSH and B-cell lymphoma 2 (Bcl-2) expression. These outcomes were linked to inhibition of Nrf2/HO-1 signaling and activation of the TLR4/NF-κB/p38 MAPK/Caspase-3 pathway. Co-treatment with APRE at 20 mg/kg/day for 21 days markedly improved all biochemical and pathological alterations evoked by MTX, demonstrating significant nephroprotective effects. Apremilast inhibits methotrexate’s harmful effects on the kidneys by activating signaling cascades that include Nrf2/HO-1, while simultaneously downregulating TLR4/NF-κB/p38 MAPK/Caspase-3.