A PDE1 inhibitor, vinpocetine, ameliorates epithelial-mesenchymal transition and renal fibrosis in adenine-induced chronic kidney injury in rats by targeting the DNMT1/Klotho/ß-catenin/Snail 1 and MMP-7 pathways.

Tubulointerstitial fibrosis (TIF) is present with chronic kidney disease (CKD). Vinpocetine (Vinpo) is used for treating cerebrovascular deficits, exhibiting some kidney-beneficial effects; however, its role in TIF is uncertain. So, the aim of this study was to investigate its potential impact on adenine-induced fibrotic CKD and explore the underlying mechanistic aspects. Eighteen male Wistar rats were categorized into three groups (n = 6 each). Group I was kept as controls and given saline; group II received adenine (300 mg/kg, twice weekly, i.p.) for induction of the CKD model; and group III was administered Vinpo (20 mg/kg/d, orally) concurrently with adenine. All treatments were administered for 4 weeks. Vinpo revealed an improvement in renal function and an alleviation of inflammation triggered by adenine via diminishing serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels. Further, Vinpo repressed the epithelial-mesenchymal transition (EMT) with preserved E-cadherin mRNA expression and lowered gene and immune expression of fibronectin and vimentin, respectively, besides attenuating the elevated G2/M arrest-related molecules (renal Ki67 protein contents and p21 gene expression). Renal pathological alterations caused by adenine were attenuated upon Vinpo administration. Interestingly, Vinpo suppressed abnormal renal ß-catenin immunoreactivity, Snail 1, and MMP-7 gene expression while simultaneously restored Klotho protein expression by downregulating DNA methyltransferase 1 enzyme (DNMT1) protein expression in the kidney. These data indicated that Vinpo effectively mitigated EMT and G2/M arrest-induced renal fibrosis in adenine-induced CKD rats by targeting DNMT1-associated Klotho suppression, subsequently inhibiting ß-catenin and its fibrotic downstream genes.

Elevated liver transaminases among patients with psychiatric disorders.

Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. To assess transaminitis among psychiatric patients treated by AD. This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Among the 135 patients, 104 (77.0%) were males. Their age was 32 ±â€…9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (

Effects of Diclofenac Versus Meloxicam in Pentylenetetrazol-Kindled Mice.

Epilepsy comes after stroke as the most common chronic neurological disorder worldwide. Inflammation enhances neuronal hyperexcitability that could provide a background setting for the development of epilepsy. The aim of this study was to assess the effect of valproate (VAL), diclofenac (DIC), meloxicam (MEL), VAL + MEL and VAL + DIC in pentylenetetrazol (PTZ) kindled mice. Seventy mice were randomly allocated into 7 equal groups; Control, PTZ, VAL, DIC, MEL, VAL + MEL and VAL + DIC groups. Kindling was induced by PTZ (40 mg/kg, i.p.) injection every other day for 17 days. The drugs were administered, 30 min before each PTZ injection till the end of the schedule. Seizure score, latency, duration and mortality rate were recorded in all groups. Tumor necrosis factor- α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA) and prostaglandin E2 (PGE2) levels as well as reduced glutathione (GSH) content were assessed in brain homogenate at the end of the schedule. VAL, DIC, MEL, VAL + MEL and VAL + DIC decreased seizure score and duration. Meanwhile, they increased the latency period. PTZ increased TNF-α, IL-1ß, MDA, and PGE2 levels meanwhile, it decreased GSH content. Administration of VAL, DIC, MEL, VAL + MEL and VAL + DIC decreased TNF-α, IL-1ß, MDA, and PGE2 levels meanwhile, they increased GSH content in the brain homogenates. Effects of VAL + DIC combination on the studied parameters were significant in relation to VAL. VAL, DIC, MEL, VAL + MEL and VAL + DIC produced anticonvulsant effect and mitigated inflammation and oxidative stress in PTZ-kindled mice. Interestingly, DIC rather than MEL enhanced the anticonvulsant effect VAL.