The Effect of Cytoprotective Agents in Platinum Anticancer Therapy
Astrid Sigel, Helmut Sigel in Metal Ions in Biological Systems, 2004
When clinical trials of cisplatin were initiated in the early 1970s, its therapeutic effects turned out to be associated with severe dose-limiting renal toxicity. Nephrotoxicity is caused by an impairement of reabsorption in the proximal and distal tubules, resulting in a markedly decreased glomerular filtration rate [1]. It is often characterized by increased mineral excretion including hypomagnesemia which is observed in about 40% of patients and also known to become permanent. Nephrotoxicity is the major cause of acute and chronic toxicity and as well as toxicity-related mortality, and it is the most common dose-limiting factor often leading to irreversible kidney damage [2]. In fact, this toxicity has severely hampered early clinical development and even led to the opinion that cisplatin might be “too interesting a drug to drop, but too dangerous for extensive use” [3]. This dilemma could only be solved, and administration of cisplatin doses, which are now routinely applied, has only become acceptable, since vigorous pre-hydration and concomitant mannitol-induced diuresis have been found to efficiently ameliorate this nephrotoxicity [4]. However, this method does not significantly lessen the other adverse effects of cisplatin, such as neurotoxicity, ototoxicity, and gastrointestinal toxicity which are frequently observed and may substantially worsen the patients’ quality of life.
EFFECT OF Plectranthus wightii METHANOL EXTRACT AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN RAT
V. R. Mohan, A. Doss, P. S. Tresina in Ethnomedicinal Plants with Therapeutic Properties, 2019
Nephrotoxicity is one of the most common kidney problems. It occurs when a body is exposed to a drug or toxin (Porter, 1981). A number of therapeutic agents can adversely affect the kidney resulting in acute renal failure, chronic interstitial nephritis, and nephritic syndrome because there is an increasing number of potent therapeutic drugs such as aminoglycoside antibiotics, NSAIDs, and chemotherapeutic agents that have been added to the therapeutic arsenal in recent years. Exposure to chemical reagents such as ethylene glycol, carbon tetrachloride, sodium oxalate, and heavy metals such as lead, mercury, cadmium, and arsenic also induces nephrotoxicity. Prompt recognition of the disease and cessation of responsible drugs are usually the only necessary therapy. Nephroprotective agents are the substances which possess protective activity against nephrotoxicity.
Antiviral therapeutics for viral infections of the central nervous system
Avindra Nath, Joseph R. Berger in Clinical Neurovirology, 2020
Foscarnet has been associated with significant renal toxicity, and dose adjustments are necessary when the creatinine clearance is ≤1.4 mL min−1 kg−1. Prehydration with saline has been shown to reduce the incidence of nephrotoxicity, as has avoidance of concurrent nephrotoxic therapy [39,40]. Nephrotoxicity and electrolyte disturbances are the major side effects associated with foscarnet. Serum creatinine elevations of up to three-fold are observed in about half of recipients. Risk factors for renal dysfunction include preexisting renal disease and concurrent use of other nephrotoxic drugs. In addition, factors such as hydration status and manner of infusion also affect nephrotoxicity [41]. Renal toxic effects are typically reversible within 2–4 weeks of discontinuing therapy. Foscarnet is a chelating agent that can cause significant electrolyte abnormalities, including hypo- and hypercalcemia and hypo- and hyperphosphatemia [42]. Hypocalcemia is seen in up to a third of patients, and can result in seizures, tetany, and arrhythmias. Hypomagnesemia and hypokalemia can also occur in some patients. CNS side effects include headache, seizures, hallucinations, tremors, and neuropathies. Other adverse effects include fever, nausea, vomiting, hepatic dysfunction, and cytopenias [1].
Ameliorative effect of a standardized polyherbal combination in methotrexate-induced nephrotoxicity in the rat
Published in Pharmaceutical Biology, 2020
Sanchit Sharma, Sanjula Baboota, Saima Amin, Showkat R. Mir
Nephrotoxicity signifies a condition of renal dysfunction that arises due to exposure to environmental chemicals or drugs. Oxidative stress and inflammation are the main pathological pathways involved in its aetiology, among others. A multifactorial condition like nephrotoxicity demands for a multipronged treatment modality for its mitigations. In this context, our current study aimed to develop a polyherbal combination for the amelioration of drug-induced nephrotoxicity. Four traditionally used Indian Medicinal plants were selected for this study. The extracts were characterized through their total phenolic content, flavonoid content and HPLC analysis. The parameters to maximize extraction efficiency were optimized using RSM. The different combinations were developed by randomized block design and screened for their XO inhibition potential and antioxidant activity. Out of these, the two best combinations were selected and tested against methotrexate-induced nephrotoxicity in rats to generate scientific data in support of in vitro results and their traditional claims.
Further insights into the impact of rebamipide on gentamicin-induced nephrotoxicity in rats: modulation of SIRT1 and β-catenin/cyclin D1 pathways
Published in Drug and Chemical Toxicology, 2023
Heba S. Zaky, Somaia A. Abdel-Sattar, Albatoul Allam, Hebatalla I. Ahmed
Gentamicin (GM) is an effective antibiotic administered to treat acute and life-threatening infections caused by Gram-negative microorganisms (Ahmed and Mohamed 2019). To date, GM is used despite its negative side effects, such as nephrotoxicity and ototoxicity (Mahi-Birjand et al.2020). Nephrotoxicity is primarily caused by the accumulation of the drug in the proximal tubular cells (Lopez-Novoa et al.2011, Randjelovic et al.2017). The drug causes a variety of adverse effects in these cells, including excessive oxidative stress, inflammation, apoptosis, and phospho-lipidosis, in addition to mitochondrial dysfunction. These events may eventually cause tubular dysfunction, cell death, and decreased glomerular filtration rate (GFR) (Martínez-Salgado et al.2007, Lopez-Novoa et al.2011, Abd-Elhamid et al.2018). As a result, medications that control oxidative stress, inflammation, and apoptosis could be used to prevent GM-induced nephrotoxicity (Famurewa et al.2020).
Nephroprotective effect of ferulic acid on gentamicin-induced nephrotoxicity in female rats
Published in Drug and Chemical Toxicology, 2022
Vasfiye Erseçkin, Handan Mert, Kıvanç İrak, Serkan Yildirim, Nihat Mert
Gentamicin is the most commonly used antibiotic amongst the aminoglycoside group of antibiotics (Reiter et al.2002). Depending on the dose and duration of administration, it causes widespread damage to the kidneys. Entering the proximal tubule cells by endocytosis, gentamicin accumulates in the lysosome, Golgi and endoplasmic reticulum. When it reaches the threshold, it discharges into the cytosol and disrupts the function of mitochondria, leading to apoptosis and necrosis (Wargo and Edwards 2014). Gentamicin is being used to produce acute kidney damage in test animals in numerous types of studies (Ataman et al.2018, Yilmaz et al.2018). Renal damage is evaluated by histopathological examinations and by measuring the levels of renal biomarkers such as BUN, creatinine, cystatin C in the serum. Increased serum creatinine and BUN levels, decreased glomerular filtration, and decreased concentration ability are interpreted as nephrotoxicity. It has been suggested that the increase in serum urea and creatinine levels are caused by decreased glomerular filtration (Ural et al.2004). The developing nephrotoxicity is mostly non-oliguric. It is known that nephrotoxicity is caused by the accumulation of the drug in the renal cortex and that the process includes pathological conditions such as renal concentration impairment, acute tubular necrosis, or renal insufficiency (Başhan 2009).
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