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.

Background: Cytochrome P450 2J2 (CYP2J2) has been implicated in tumor biology, but its expression pattern and clinical significance in prostate and renal cancers remain poorly characterized. Methods: Commercially available tissue microarrays containing 208 renal and 121 prostate tissue specimens were used for immunohistochemical (IHC) characterization of CYP2J2 protein expression. We performed transcriptomic analysis and examined correlations with clinicopathological features and survival using the OncoDB 2.0 platform. Results: CYP2J2 immunoreactivity was mainly cytoplasmic, with minimal protein expression in both cancers. We identified positive staining in 7/100 (7.0%) prostate adenocarcinomas and 2/192 (1.0%) clear cell renal cell carcinoma (ccRCC) specimens, with negative expression in corresponding normal tissues. We detected no significant associations between protein expression and clinicopathological features in either cohort (all p > 0.05). In contrast, transcriptomic analysis revealed elevated CYP2J2 mRNA expression in both malignancies, with a slight increase in prostate adenocarcinoma (log₂ fold change = 1.10) and marked overexpression in ccRCC (log₂ fold change = 5.24) compared with normal tissues. We observed significant associations between CYP2J2 mRNA expression and pathological T stage in prostate adenocarcinoma (p = 0.0019) and pathological M stage in ccRCC (p = 0.0079). Moreover, higher CYP2J2 mRNA expression was associated with longer overall survival in ccRCC (HR = 0.64, 95% CI: 0.47–0.86; log-rank p = 0.0029) but not in prostate adenocarcinoma; however, these findings remain exploratory and do not establish independent prognostic value. Conclusions: Despite elevated transcript expression, CYP2J2 protein expression was infrequent in prostate adenocarcinoma and ccRCC, suggesting limited clinicopathological relevance and warranting further investigation using functional techniques.