Effect of free creatine therapy on cisplatin-induced renal damage

Abstract

Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n ¼ 20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin + creatine monohydrate (n ¼ 20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n ¼ 20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p50.05). In group II, there was a slight decrease in body weight at same days (p ¼ 0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p50.05). Although creatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

“…By delaying the depletion of ATP during oxygen deprivation and reducing the availability of ROS (Balestrino et al 1999), pretreatment with creatine can reduce the cardiac and neurological damages induced by ischemia or anoxia and that such treatment can also be useful even after the onset of stroke or myocardial infarction (Balestrino et al 2002;Lensman et al 2006;Osbakken et al 1992;Perasso et al 2013;Prass et al 2007;Scheer et al 2016;Shen and Goldberg 2012;Whittingham and Lipton 1981;Wilken et al 1998;Zapara et al 2004). Of note, creatine has been safely and beneficially administered to patients affected by age-related neurological diseases, including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, long-term memory deficits, Alzheimer's disease, and stroke (Adhihetty and Beal 2008; Smith et al 2014), as well as patients with pathophysiological conditions, such as gyrate atrophy, post-stroke depression, congestive heart failure, chronic musculoskeletal pain disorders, atherosclerotic diseases, and cisplatin-induced renal damage (Genc et al 2014;Hummer et al 2019;Persky and Brazeau 2001;Wyss and Schulze 2002). Through increasing the availability of arginine for the generation of nitric oxide (a killer of pathogenic bacteria, fungi, parasites, and viruses), dietary supplementation with creatine plays an important role in protecting humans from infectious diseases (Ren et al 2018).…”

A review of creatine supplementation in age-related diseases: more than a supplement for athletes

“…In addition to athletic performance, creatine usage has expanded to treat pathophysiological conditions including gyrate atrophy, post-stroke depression, congestive heart failure, chronic musculoskeletal pain disorders, atherosclerotic diseases and cisplatin nephrotoxicity 28 , 46 , 47 . Furthermore, a recent review proposed prophylactic creatine supplementation could reduce chances of preterm labor or hypoxic-ischemic encephalopathy 48 .…”

Defining cisplatin incorporation properties in thermosensitive injectable biodegradable hydrogel for sustained delivery and enhanced cytotoxicity

“…It interacts with guanine and adenine N7 atoms located in the DNA major groove, leading to DNA bending and interfering with its replication, transcription as well as other nuclear functions, thus, arresting cancer cell proliferation and tumor growth (Cepeda et al, 2007). Despite its clinical success, intravenous Cis administration can lead to nephrotoxicity, bone marrow toxicity, intractable vomiting, peripheral neuropathy, deafness, seizures and blindness (Genc et al, 2014;Wang et al, 2014). Drug resistance during therapy is another important limitation to its use requiring the use of increasing doses (Dzamitika et al, 2006).…”