Gad Elsayed Mohamed Salem

This study investigated the protective effects of vitamin C against linezolid-induced hepatotoxicity and nephrotoxicity in rats using biochemical, histopathological, and immunohistochemical methods. Twenty-four rats were divided into four groups: control, linezolid (100 mg/kg/day), vitamin C (100 mg/kg/day), and a combination of vitamin C and linezolid for 14 days. Linezolid treatment resulted in lactic acidosis, increased serum levels of AST, ALT, urea, creatinine, and albumin, and oxidative stress characterized by decreased catalase activity and reduced glutathione (GSH) associated with increased nitric oxide (NO) malondialdehyde (MDA). Pro-inflammatory markers (IL-1β, TNF-α) and renal CD68 expression also increased. Linezolid disrupted autophagy (reduced Beclin-1 levels) and induced apoptosis through hyperactivation of Wingless/integrated (Wnt) signaling (increased Wnt 7a and Wnt 10a expression). Treatment with vitamin C alleviated linezolid side effects by reducing AST, ALT, urea, creatinine, lactic acid, IL-1β, TNF-α, NO, MDA, and Wnt signaling markers while increasing albumin, catalase, GSH, and Beclin-1 levels. Histopathological and immunohistochemical analyses confirmed significant protection of liver and kidney tissues in rats co-administered vitamin C with linezolid. These results suggest that vitamin C can effectively alleviate hepatotoxicity and nephrotoxicity caused by linezolid.

Cefotaxime is a broad-spectrum antibiotic targeting Gram-negative bacteria used for diverse infections, but it can be toxic to the stomach, liver, and kidneys. This study explored the protective effects of geranium oil against cefotaxime-induced hepatotoxicity and nephrotoxicity in rats, employing biochemical, histopathological, and immunohistochemical evaluations. Thirty rats were divided into five groups of six animals each one. Group 1 received orally normal saline for 14 days, Group 2 was given orally 2.5% DMSO for 14 days, Group 3 received cefotaxime (200 mg/kg/day IM) for 14 days, Group 4 received with cefotaxime (200 mg/kg/day IM) and geranium oil (67 mg/kg b. w./day orally in DMSO) for 14 days, and Group 5 received geranium oil alone (67 mg/kg b. w./day orally in DMSO) for 14 days. Geranium oil significantly reduced cefotaxime-induced damage, evidenced by lower serum levels of liver enzymes (AST, ALT), renal markers (urea, creatinine), and other indicators (alkaline phosphatase, TNF-alpha, IL-1Beta, MAPK, nitric oxide, MDA). It also increased levels of protective tissue biomarkers such as NrF2, albumin, catalase, Beclin 1, and reduced glutathione (GSH). Histopathological and immunohistochemical analyses revealed significant protective effects in liver and renal tissues in rats treated with Geranium oil. These results suggest that Geranium oil is effective in mitigating cefotaxime-induced hepatotoxicity and renal toxicity.

The present study demonstrates the production and thrombolytic potential of a novel thermostable thiol-dependent fibrinolytic protease by Bacillus cereus RSA1. Statistical optimization of different parameters was accomplished with Plackett–Burman design and validated further by central composite design with 30.75 U/mL protease production. Precipitation and chromatographic approaches resulted in 33.11% recovery with 2.32-fold purification. The molecular weight of fibrinolytic protease was 40 KDa and it exhibited a broad temperature and pH stability range of 20–80 °C and pH 5–10 with utmost activity at 50 °C and pH 8, respectively. The protease retained its fibrinolytic activity in organic solvents and enhanced the activity in solutions with divalent cations (Mn²⁺, Zn²⁺, and Cu²⁺). The enzyme kinetics revealed K_m and V_max values of 1.093 mg/mL and 52.39 µg/mL/min, respectively, indicating higher affinity of fibrinolytic activity towards fibrin. Also, complete inhibition of fibrinolytic activity with DFP and a 2-fold increase with DTT and β-mercaptoethanol indicates its thiol-dependent serine protease nature. MALDI–TOF analysis showed 56% amino acid sequence homology with Subtilisin NAT OS = Bacillus subtilis subsp. natto. The fibrinolysis activity was compared with a commercial thrombolytic agent for its therapeutic applicability, and fibrinolytic protease was found highly significant with absolute blood clot dissolution within 4 h in in vitro conditions. The isolated fibrinolytic protease of Bacillus cereus RSA1 is novel and different from other known fibrinolytic proteases with high stability and efficacy, which might have wide medicinal and industrial application as a thrombolytic agent and in blood stain removal, respectively.