Piribedil and thymol mitigate vancomycin-evoked nephrotoxicity in rats through modulation of Keap-1/Nrf2/HO-1 and NF-κB/Bax/caspase 3 signalings
Creators: name: Yahia, Rania
name: Hassan, Gehad Gamal
name: Abo-Youssef, Amira M.
name: Mahmoud, Heba M.
Publisher: name: Taylor & Francis
Year: 2025
Subjects: subject: Biochemistry
subject: Medicine
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Physiology
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Developmental Biology
subject: Marine Biology
subject: Cancer

description: Nephrotoxicity is a sign in which endogenous or exogenous toxicants have damaged the kidney-specific detoxification and excretion processes. Vancomycin (VAN) exposure mostly causes kidney damage and a loss of body homeostasis regulation. This study aimed to investigate the protective effects of piribedil and thymol and its basic mechanisms against nephrotoxicity caused by VAN. Randomly, the animals were categorized into six groups (<i>n</i> = 8). For 7 d, Group I only received vehicles, Group II received piribedil (5 mg/kg/once daily, i.p.), Group III received thymol (25 mg/kg/once daily, i.p), Group IV was administered a single daily dose of VAN (200 mg/kg, i.p.), VAN+ piribedil was administered to Group V, and VAN + thymol was administered to Group VI. The findings showed that piribedil or thymol improved renal function parameters by an increase in serum albumin level in parallel to a decrease in serum creatinine and blood urea nitrogen (BUN) levels in addition to decreased levels of KIM-1 and serum cystatin C. Furthermore, enhanced oxidative stress biomarkers as GSH, myeloperoxidase (MPO), and malondialdehyde (MDA) as well as tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), indicators of inflammatory mediators, were markedly reduced compared to VAN group. Moreover, piribedil or thymol markedly improved the histopathological aberrations provoked by VAN, increased the Nrf-2 and HO-1 renal protein expressions and reduced VAN-induced elevation of Keap-1 protein expression. In addition, NF-kB, Bax, and caspase 3 expression levels were considerably declined after piribedil or thymol co-treatment. These findings revealed that co-administration of piribedil or thymol with VAN may be a sensible therapeutic approach for reducing renal intoxication caused by VAN. Piribedil or thymol co-treatment improved renal impairment and histological alterations induced by vancomycin.Piribedil or thymol co-treatment alleviated vancomycin-induced oxidative damage by reducing malondialdehyde (MDA) and myeloperoxidase (MPO) as well as restoring GSH renal contents.Piribedil or thymol co-treatment mitigated vancomycin-evoked inflammation and apoptosis.The beneficial effects of piribedil or thymol could be mediated via modulation of Keap-1/Nrf2/HO-1 and NF-kB/Bax/caspase 3 signaling pathways. Piribedil or thymol co-treatment improved renal impairment and histological alterations induced by vancomycin. Piribedil or thymol co-treatment alleviated vancomycin-induced oxidative damage by reducing malondialdehyde (MDA) and myeloperoxidase (MPO) as well as restoring GSH renal contents. Piribedil or thymol co-treatment mitigated vancomycin-evoked inflammation and apoptosis. The beneficial effects of piribedil or thymol could be mediated via modulation of Keap-1/Nrf2/HO-1 and NF-kB/Bax/caspase 3 signaling pathways. Piribedil or thymol ameliorated vancomycin-induced renal injury by improving the Nrf2 and HO-1 renal protein expressions and reduced VAN-induced elevation of keap1 protein expression. In addition, considerable decrease in NF-kB, Bax, and caspase 3 expression levels.