Fisetin Treats Kidney Oxidative Stress, Inflammation, and Apoptosis in Rat Diarrhea.

ABSTRACT

BACKGROUND: Diarrhea is the increase in the excretion of human water; meanwhile, fisetin, a bioactive flavonol molecule, is widely used in the treatment/prevention of gastrointestinal disorders. The purpose of this study is to investigate the anti-diarrheal activity of fisetin by restoring kidney function, antioxidant activity, inflammatory markers, Na+/K+-ATPase level, apoptosis, and protein content in diarrheal rats. METHODS: A total of 36 male rats were distributed into two groups (18 rats/group) normal and diarrheal. The normal group was further divided into three subgroups (6 rats/subgroup) Control, fisetin, and desmopressin drug subgroups, consisting of normal rats orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. A lactose diet containing 35% lactose was fed to the normal rats for a month. The diarrheal rats were also divided into three subgroups (6 rats/subgroup) diarrheal rats, diarrheal rats + fisetin, and diarrheal rats + desmopressin drug groups, whereby the diarrheal rats were orally treated once a day for 4 weeks with 1 mL distilled water, 50 mg/kg fisetin, and 1 mg/kg desmopressin drug, respectively. RESULTS: Fisetin significantly decreased serum urea (41.20 ± 2.6-29.74 ± 2.65), creatinine (1.43 ± 0.05-0.79 ± 0.06), and urinary volume (1.30 ± 0.41-0.98 ± 0.20), while significantly increasing kidney weight (0.48 ± 0.03-0.67 ± 0.07), sodium, potassium, and chloride balance in both serum and urine. Fisetin significantly increased the antioxidant activity (superoxide dismutase (1170 ± 40-3230 ± 50), glutathione peroxidase (365 ± 18-775 ± 16), catalase (0.09 ± 0.03-0.14 ± 0.06), and nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase activity (8.6 ± 1.31-10.5 ± 1.25), while significantly decreasing malondialdehyde (19.38 ± 0.54-9.54 ± 0.83), conjugated dienes (1.86 ± 0.24-1.64 ± 0.19), and oxidative index (0.62 ± 0.04-0.54 ± 0.05)), alongside the inflammatory markers (tumor necrosis factor-α (65.2 ± 2.59-45.3 ± 2.64), interleukin-1ß, interleukin-6 (107 ± 4.5-56.1 ± 7.2), and interleukin-10) in the diarrheal rats to values approaching the control values. Fisetin also restored the Na+/K+-ATPase level, apoptosis, protein content, and kidney architecture in diarrheal rats to be near the control group. CONCLUSIONS: Fisetin treated diarrhea in rats by restoring kidney function, antioxidant activity, inflammatory markers, apoptosis, proteome content, and histology.