Drug-induced Kidney Disease – Pathology and Current Concepts

Loh, Alwin Hwai-Liang; Cohen, Arthur H.

doi:10.47102/annals-acadmedsg.v38n3p240

Cited by 39 publications

(3 citation statements)

References 111 publications

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“…Among the various forms of AKI, drug-induced AKI is a common concern in clinic [2]. Kidneys are primarily involved in filtering and concentrating various substances and chemical agents [3]. Acetaminophen (APAP), an analgesic and antipyretic agent, is better known as paracetamol in many countries.…”

Section: Introductionmentioning

confidence: 99%

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation

et al. 2018

Kidney Blood Press Res

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Background/Aims: In clinic, excessive acetaminophen (APAP) can cause kidney damage with uncertain mechanisms. Recently, accumulating evidence demonstrated a pathogenic role of mitochondrial dysfunction in the kidney injury. Thus, in this study, rotenone, a mitochondrial complex I inhibitor, was applied to the mice with APAP-induced acute kidney injury to evaluate the effect of mitochondrial complex I inhibition on APAP nephrotoxicity. Methods: After 3 days of rotenone pretreatment, mice were administered with APAP (300mg/kg) by intraperitoneal injection for 24 h. Then the kidney injury, inflammation, and oxidative stress were evaluated. Results: APAP significantly enhanced the BUN, serum creatine, and cystatin C levels in line with a moderate alteration of renal morphology. Strikingly, rotenone treatment normalized BUN, serum creatinine, and cystatin C levels, as well as the kidney morphology. Meanwhile, APAP enhanced tubular injury markers of NGAL and KIM-1 by 347- and 5-fold at mRNA levels, respectively. By Western blotting, we confirmed a 15-fold increment of NGAL in APAP-exposed kidneys. Importantly, rotenone treatment largely normalized NGAL and KIM-1 levels and attenuated inflammatory response in APAP-treated mice. Similarly, rotenone treatment enhanced the expressions of SOD1-3 compared with APAP group in line with a significant suppression of kidney MDA content. Finally, we observed that inhibition of mitochondrial complex III failed to protect against APAP-induced nephrotoxicity. Conclusion: Mitochondrial complex I inhibitor rotenone protected kidneys against APAP-induced injury possibly via the inhibition of mitochondrial oxidative stress and inflammation.

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Section: Introductionmentioning

confidence: 99%

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation

et al. 2018

Kidney Blood Press Res

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“…Studies have reported that prolonged use of certain classes of antibiotics such as fluoroquinolones, aminoglycosides, β-lactams, and glycopeptides in diseased conditions may exert detrimental effects, some of which are strongly associated with various renal diseases such as interstitial nephropathy, tubular cell toxicity, and tubulointerstitial fibrosis [ 8 , 43 , 44 ]. Also, it has been well speculated that misuse or overuse of such antibiotics might compromise the body’s immune system to fight against diseases and may contribute to further exaggerated complications [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Prolonged Antibiotic Use in a Preclinical Model of Gulf War Chronic Multisymptom-Illness Causes Renal Fibrosis-like Pathology via Increased micro-RNA 21-Induced PTEN Inhibition That Is Correlated with Low Host Lachnospiraceae Abundance

Trivedi,

Bose,

Saha

et al. 2023

Cells

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Gulf War (GW) veterans show gastrointestinal disturbances and gut dysbiosis. Prolonged antibiotic treatments commonly employed in veterans, especially the use of fluoroquinolones and aminoglycosides, have also been associated with dysbiosis. This study investigates the effect of prolonged antibiotic exposure on risks of adverse renal pathology and its association with gut bacterial species abundance in underlying GWI and aims to uncover the molecular mechanisms leading to possible renal dysfunction with aging. Using a GWI mouse model, administration of a prolonged antibiotic regimen involving neomycin and enrofloxacin treatment for 5 months showed an exacerbated renal inflammation with increased NF-κB activation and pro-inflammatory cytokines levels. Involvement of the high mobility group 1 (HMGB1)-mediated receptor for advanced glycation end products (RAGE) activation triggered an inflammatory phenotype and increased transforming growth factor-β (TGF-β) production. Mechanistically, TGF-β- induced microRNA-21 upregulation in the renal tissue leads to decreased phosphatase and tensin homolog (PTEN) expression. The above event led to the activation of protein kinase-B (AKT) signaling, resulting in increased fibronectin production and fibrosis-like pathology. Importantly, the increased miR-21 was associated with low levels of Lachnospiraceae in the host gut which is also a key to heightened HMGB1-mediated inflammation. Overall, though correlative, the study highlights the complex interplay between GWI, host gut dysbiosis, prolonged antibiotics usage, and renal pathology via miR-21/PTEN/AKT signaling.

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“…The kidneys are highly vulnerable to the harmful influences of chemicals and medications because they are actively responsible for filtering and concentrating various substances and chemicals that may accumulate to high dangerous concentrations, which frequently result in the formation of reactive metabolites that are now regarded as key players in the pathogenesis of a renal injury [ 38 , 39 ]. The kidney is a unique organ for NP targeting because of its inherent ability to quickly remove particles with a diameter < 10 nm [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats

Aboelwafa

Ramadan

Ibraheim

et al. 2022

Biology

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The use of silver nanoparticles (AgNPs) is expanding. This study evaluates the modulator effect of eugenol (Eug) on AgNP-induced nephrotoxicity in rats. Sixty male rats were separated into six groups: control, Eug, AgNPs low-dose, AgNPs high-dose, Eug + AgNPs low-dose, and Eug + AgNPs high-dose. After 30 days, kidney function, antioxidative and proinflammatory status, histopathological, histomorphometrical, and immunohistochemical assessments were performed. AgNPs markedly induced oxidative stress in renal tissues, characterized by increased levels of blood urea nitrogen, creatinine, uric acid, kidney injury molecule-1, the total oxidant capacity, malondialdehyde, tumor necrosis factor-alpha (TNF-α), and interleukin-6, as well as decreased levels of the total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, and glutathione peroxidase. Moreover, the normal renal architecture was destroyed, and the thickness of the renal capsules, cortex, and medulla, alongside the diameter and quantity of the normal Malpighian corpuscles and the proximal and distal convoluted tubules were decreased. Immunoreactivity for P53, caspase-3, and TNF-α reactive proteins were significantly increased; however, Bcl-2 immunoreactivity was decreased. Eug reversed most biochemical, histological, histomorphometrical, and immunohistochemical changes in AgNP-treated animals. This study demonstrated that nephrotoxicity in AgNP-treated rats was mitigated by an Eug supplementation. Eug’s antioxidant, antiapoptotic, and anti-inflammatory capabilities were the key in modulating AgNPs nephrotoxicity.

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Drug-induced Kidney Disease – Pathology and Current Concepts

Cited by 39 publications

References 111 publications

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation

Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating Oxidative Stress and Inflammation

Prolonged Antibiotic Use in a Preclinical Model of Gulf War Chronic Multisymptom-Illness Causes Renal Fibrosis-like Pathology via Increased micro-RNA 21-Induced PTEN Inhibition That Is Correlated with Low Host Lachnospiraceae Abundance

Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats

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