Cefepime and diclofenac sodium combined treatment‐potentiated multiple organ injury: Role of oxidative damage and disrupted lipid metabolism

Abstract

Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3

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

“…Surprisingly, according to the current histological study, the proximal tubules were the most affected areas of the kidneys following Cd intoxication. These findings are consistent with our prior research, which indicates the vulnerability of the cortical region to oxidative degradation caused by different insults such as gentamicin ( Abdeen et al, 2021 ), cefepime ( Aboubakr et al, 2021a ), and aflatoxins B 1 ( Abdel-Daim et al, 2021 ). Therefore, it is strongly assumed that mitochondria constitutes a potential subcellular target for Cd ( Gobe and Crane, 2010 ).…”

“…Oxidative distress is renowned for being initiated when the produced ROS, such as superoxide anions (O 2 •− ), hydroxyl radicals (OH • ), and hydrogen peroxide (H 2 O 2 ), overrides the endogenous antioxidant's capacity ( Abdeen et al, 2019 ). Thereafter, tissue injury is elicited via provoking a cascade of complex mechanisms, such as the enhancement of LPO, protein misfolding, mitochondrial perturbation, depleted ATP production, and DNA damage ( Abdel Moneim et al, 2014 ; Aboubakr et al, 2021a ; Wang et al, 2021 ).…”

“…Furthermore, this work shows substantial reductions in albumin and globulin serum levels which in turn affect the total protein levels after Cd exposure. These reductions might be attributed to the Cd-induced inhibition of protein synthesis due to oxidative stress, endoplasmic reticulum stress, and DNA oxidation, which ended up suppressing mRNA transcription and translation processes in the hepatocytes ( El-boshy et al, 2014 ; Aboubakr et al, 2021a ). Our histopathological findings confirm the occurrence of hepatic degenerative changes in response to Cd intoxication.…”

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

“…The current findings are in complete agreement with our previous experiments. The tissue injury generated by oxidative stress-inducing agents was promoted when given in combination such as cadmium with piroxicam [41] and cefepime with diclofenac sodium [49].…”

Development and Challenges of Diclofenac-Based Novel Therapeutics: Targeting Cancer and Complex Diseases

“…In addition, adverse drug–drug interactions of diclofenac, when tested in combination with other drugs such as ACE inhibitors, antimicrobial agents, anticoagulants, and cyclosporine, have also been reported. A recently concluded study in mice found the concomitant use of cefepime and diclofenac led to multiple organ failure [ 148 ]. The potential of diclofenac as an antimicrobial agent, anticonvulsant, amyloid inhibitor, and anticancer agent has been proposed and tested.…”