No 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.

Patients treated with cyclophosphamide (CP) usually suffer from severe hemorrhagic cystitis (HC). Our previous study exhibited that mesna + celery cotherapy partially ameliorated HC. Therefore, there is a substantial need to seek alternative regimens to get complete protection against CP-induced HC. The current study investigated the effects of mesna + celery seed oil (MCSO) or mesna + manuka honey (MMH) cotherapy against CP-induced HC in adult male rabbits. The forty rabbits were divided into four equal groups and treated for three weeks. The control group (G1) received distilled water and the second group (G2) received CP (50 mg/kg/week). The third group (G3) received CP + MCSO (CPMCSO regimen), and the fourth group (G4) received CP + MMH (CPMMH regimen). The urinary bladder (UB) specimens were processed to evaluate UB changes through histopathological, immunohistochemical, ultrastructural, and biochemical investigations. In G2, CP provoked HC features (urothelial necrosis, ulceration, and sloughing), UB fibrosis, and TNF-α immunoexpression. Besides, CP reduced the activity of antioxidant enzymes (GPx1, SOD3, and CAT) and elevated the serum levels of NF-κB, TNF-α, IL-1B, and IL-6 cytokines in G2 rabbits. In contrast, the CPMMH regimen caused significant increments of UB protection against HC in G4 rabbits compared to the partial protection by the CPMCSO regimen in G3. Therefore, our study indicated for the first time that the novel CPMMH regimen resulted in complete UB protection against CP-induced HC via combined antioxidant, anti-inflammatory, and antifibrotic properties.