Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay

Abstract

Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.

Gentamicin potentiate tigecycline induced cardiotoxicity in rats: the cardiac susceptibility to oxidative stress

“…In tigecycline-treated cells, oxidative damage to DNA, protein, and lipid was observed, which is consistent with oxidative stress (Tan et al, 2017). Previous research demonstrated the existence of DNA damage and repair processes brought on by TIG and/or GEN therapy (Elgazzar et al, 2022). Pathological research on rabbits demonstrated that longterm GEN administration causes myocardial muscle cell congestion and necrosis, which would be linked to inadequate systemic circulation (Saleh, 2018).…”

“…These data corroborate and broaden previous research indicating a link among oxidative stress and TIGinduced cardiotoxicity. It was demonstrated that TIG causes increased ROS creation as well as protein damage measurements (Elgazzar et al, 2022). Tigecycline raises levels of mitochondrial superoxide, hydrogen peroxide, and (ROS).…”

The Combination of Tamarindus indica and Coenzyme Q10 can be a Potential Therapy Preference to Attenuate Cadmium-Induced Hepatorenal Injury

“…Cd promotes mitochondrial deterioration leading to reduction in ATP synthesis and incremented reactive oxygen species (ROS) generation ( Mirkov et al, 2021 ). As a result, mitochondrial dysfunction, peroxidation of membrane lipid (LPO), protein misfolding, DNA oxidation, and ultimately, overture of apoptotic pathways are instigated ( Abdeen et al, 2019 ; Mirkov et al, 2021 ; Elgazzar et al, 2022 ).…”

Microalgae (Chlorella vulgaris) attenuates aflatoxin-associated renal injury

“…There is ample proof indicating the embroilment of oxidative stress, inflammatory responses, and apoptotic pathway in AFT-induced nephrotoxicity ( Owumi et al, 2020 ; Wang et al, 2022 ). Thus, excess generation of reactive oxygen species (ROS), with consumption of antioxidant enzymes after AFT intoxication, provokes tissue injuries such as DNA mutations, mitochondrial disruption, improper folding of protein, and ultimately necroptosis ( Dlamini et al, 2021 ; Elgazzar et al, 2022 ; Li et al, 2022 ). Moreover, the stability of AFTs and their metabolites highlights the necessity for developing secure, feasible, and efficient strategies for reducing their damaging impacts ( Kolosova and Stroka, 2012 ).…”