Glycine protects against doxorubicin-induced heart toxicity in mice

Abstract

Doxorubicin (DOXO) is a well-known cancer chemotherapeutic. However, its toxic effect on the heart limits its clinical application. This study aimed to assess the effectiveness of glycine administration to counteract the DOXO-induction of cardiomyopathy in mice. Fifty male albino mice were divided into five groups (n = 10/group) as follows: control, DOXO, Gp100, Gp150, and Gp200. Histopathological examination of the heart, and biochemical examinations for heart function (creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST)), inflammation (tumor necrosis factor-alpha (TNF-α) and interleukin 10 (IL-10)), oxidative stress (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, nitric oxide (NO), and uric acid), kidney function (urea and creatinine), and minerals (calcium, phosphorus, sodium, and potassium) were carried out. Cardiomyopathy induced by DOXO treatment (15 mg/kg total dose) was ascertained via pathological alterations seen in heart tissue and verified biochemically via increases (P < 0.001) in CPK, LDH, AST, TNF-α, IL-10, MDA, NO, Na, and K levels along with decreases (P < 0.001) in GSH, SOD, catalase, and uric acid. Glycine co-treatment, using doses of 100, 150, and 200 mg/kg, in a dose-dependent manner, displayed ameliorated heart architecture, significantly (P < 0.001) improved biochemical heart function tests, reduced oxidative stress and inflammation, and controlled mineral levels. The positive actions of glycine in DOXO-induced cardiotoxicity amelioration via modulating oxidative stress, inflammation, and immunity are confirmed. Glycine antioxidative properties may be behind its positive outcomes. Finally, we present glycine as a worthy possible option against DOXO-induced heart damage after more validation.

The effect of Usnea longissima extract on chemotherapy-associated multi-organ damage in rats

“…Cisplatin increased MDA levels more than doxorubicin in kidney tissue. In the experiments carried out, it was shown that increasing MDA levels in tissues given doxorubicin and cisplatin is an indicator of reactive oxygen radical increase [27,28]. Our results and the data from the previous studies show that increase in LPO level has an important role in doxorubicin and cisplatin toxicity.…”

“…Determining changes in antioxidant levels is one of the most commonly used methods to evaluate oxidative damage in organs and tissues [27,30]. In our study, we investigated the level of tGSH as an endogenous antioxidant in ovarian, heart, liver and kidney tissues.…”

Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients

“…In HER2-positive breast cancer patients, a decrease in plasma glycine level was revealed 2 weeks after completion of doxorubicin treatment. Interestingly, a study in mice observed that glycine administration could protect against doxorubicin-induced cardiotoxicity [ 48 ]. Therefore, it was likely that this benefit of glycine administration was mainly due to a restoration of plasma glycine level.…”

Rifampicin efficacy against doxorubicin-induced cardiotoxicity in mice

“…To induce cardiotoxicity in mice, a cumulative dose of 15 mg doxorubicin/kg was used [ 16 , 17 ] as follows: from the stock solution of doxorubicin with a concentration of 2 mg/mL in saline, mice intraperitoneally received a doxorubicin dose of 2.5 mL/kg/day (equivalent to 5 mg/kg/day) diluted directly before injection in saline (10%, v/v) on days 1, 5, and 9 of the experiment.…”

“…days of injection Route Exp. duration Day of scarification Control Negative control – – – – – – 14 days 14 Doxorubicin Positive control (cardiotoxicity) Doxorubicin 5 [ 16 , 17 ] 3 times (4 day intervals) 1,5,9 i.p 14 days 14 Doxorubicin + Rifampicin 0.107 First treated group with rifampicin Doxorubicin 5 [ 16 , 17 ] 3 times (4 day intervals) 1,5,9 i.p 14 days 14 Rifampicin 0.107 [ 11 ] Once daily 1–14 i.p Doxorubicin + Rifampicin 0.214 Second treated group with rifampicin Doxorubicin 5 [ 16 , 17 ] 3 times (4 day intervals) 1,5,9 i.p 14 days 14 Rifampicin 0.214 – Once daily 1–14 ...…”