Probiotics Containing Lactobacillus Are Promising Candidates for Cisplatin-Induced Cardiotoxicity

Abstract

This study examined the effects of the mixture of probiotics Lactobacillus (Lactobacillus rhamnosus, Lactobacillus fermentum, and Lactobacillus brevis) against cardiotoxicity induced by cisplatin (CP) in rats by monitoring markers of oxidative stress, inflammation, and apoptosis in cardiac tissue. For this study, 28 male rats were divided into four groups as follows: Control, CP, Lactobacillus + CP, and Lactobacillus. Experimental cardiotoxicity was induced by CP. The activity of cardiac enzymes in serum and indicators of oxidative stress and nitric oxide (NO) in heart tissues were measured using biochemical methods. Inflammation, apoptosis, and DNA damage were also assessed in cardiac tissue by immunohistochemistry and immunofluorescence. CP administration caused a significant increases (p < 0.01) in malondialdehyde (1.53 +/- 0.21), NO (77.83 +/- 4.26), and 8-hydroxydeoxyguanosine (8-OHdG) (80.50 +/- 1.64) levels as well as marked decreases (p < 0.01) in the activity of superoxide dismutase (0.93 +/- 0.15) and the level of glutathione (1.87 +/- 0.20) in the CP group compared with those in the control group (0.88 +/- 0.19, 53.67 +/- 5.32, 21.67 +/- 0.81, 1.39 +/- 0.29, 2.64 +/- 0.28, respectively). This imbalance in the oxidant/antioxidant system was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha), Bcl-2-associated X protein (Bax), and caspase-3. CP also caused degenerative and necrotic changes in cardiac tissues and increased cardiac biomarkers, such as serum creatine kinase, creatine kinase myocardial band, lactate dehydrogenase, and troponin I. In contrast, the Lactobacillus probiotic administration significantly reduced (p < 0.01) malondialdehyde (1.04 +/- 0.21) and NO (56.33 +/- 5.39) levels in the Lactobacillus + CP group compared with those in the CP group, and significantly increased (p < 0.01) GSH levels (2.33 +/- 0.14) in the Lactobacillus + CP group compared with that in the CP group. Lactobacillus probiotic also decreased TNF-alpha, 8-OHdG, Bax, and caspase-3 expression, and increased the expression of B-cell lymphoma 2. This enhanced the histopathology of the heart and positively affected cardiac biomarkers. In conclusion, the probiotic Lactobacillus reversed cardiotoxicity by suppressing oxidative stress, attenuating the inflammatory process, and improving the proteins that regulate apoptosis. Our findings support the use of probiotics to treat cardiotoxicity resulting from cancer therapy with CP.