Natural Terpenes Prevent Mitochondrial Dysfunction, Oxidative Stress and Release of Apoptotic Proteins during Nimesulide-Hepatotoxicity in Rats

Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P<0.001), increased superoxide and secondary ROS/RNS generation along with oxidative damage to cellular macromolecules. Nimesulide reduced mitochondrial activity, depolarized mitochondria and caused membrane permeability transition (MPT) followed by release of apoptotic proteins (AIF; apoptosis inducing factor, EndoG; endonuclease G, and Cyto c; cytochrome c). It also significantly activated caspase-9 and caspase-3 and increased oxidative DNA damage (level of 8-Oxoguanine glycosylase; P<0.05). A combination of camphene and geraniol (CG; 1∶1), when pre-administered in rats (10 mg/kg BW), accorded protection against nimesulide hepatotoxicity in vivo, as evident from normalized serum biomarkers and histopathology. mRNA expression and activity of key antioxidant and redox enzymes along with oxidative stress were also normalized due to CG pre-treatment. Downstream effects like decreased mitochondrial swelling, inhibition in release of apoptotic proteins, prevention of mitochondrial depolarization along with reduction in oxidized NAD(P)H and increased mitochondrial electron flow further supported protective action of selected terpenes against nimesulide toxicity. Therefore CG, a combination of natural terpenes prevented nimesulide induced cellular damage and ensuing hepatotoxicity

A study of microbiology in diabetic foot infections

Background: Diabetic foot ulcers and infections are a common complication of diabetes. Holistic patient care requires dissemination of knowledge about prevention to avoid amputation and associated morbidity, early diagnosis and apt treatment. Healthcare costs of diabetic ulcers are high as complete treatment requires long term monitoring and high cost of rehabilitation in amputees. Methods: The study design is retrospective observational study. All data was retrospectively procured from the Medical Record Department. From January 2019 to December 2019, two hundred and twenty patients with diabetic foot infections who had been treated with oral or parenteral antibiotics in the previous 5 to 15 days were chosen. Results: The gram negative bacteria (88%) were most commonly isolated. Gram positive organisms contributed to 11% and candida spp. to 1% of swab culture. All patients with Staphylococci in wound swab were 100% sensitivity to vancomycin &amp; linezolid. Teicoplanin, vancomycin, and clindamycin had 100% sensitivity against MRSA in wound swab. Patients with E. coli in wound swab had maximum sensitivity to colistin. Ceftriaxone which has been used conventionally was found less sensitive for E. coli and Klebsiella. Conclusion: Piperacillin tazobactam combination for gram negative coverage in accordance to sensitivity pattern of community acquired infection is recommended because conventionally used ceftriaxone is less sensitive. For gram positive diabetic foot ulcers/ infections which were seen to be hospital acquired, linezolid is recommended for full course.</jats:p

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