Possible effects of hemp (Canabis sativa) seed oil in experimental model of myoglobinuric acute renal failure

ABSTRACT POSSIBLE EFFECTS OF HEMP (Canabis Sativa) SEED OIL IN EXPERIMENTAL MODEL OF MYOGLOBINURIC ACUTE RENAL FAILURE Tokmak D. Adnan Menderes University, The Institue of Health Sciences, Department of Physiology (Medicine) Doctoral Thesis, Aydın, 2025 Objective: Previous studies have reported that Cannabis sativa and its various parts exhibit antioxidant and anti-inflammatory properties. This study aimed to investigate the effects of hemp seed oil (Cannabis sativa) on the experimental myoglobinuric acute kidney injury (MABH) model in rats. Method: For the experiment, 60 male Wistar Albino rats weighing 260-370 g and aged 12 weeks were used, with 10 rats in each of 6 randomised groups. Kidney damage was induced on the seventh day of the study by administering 50% hypertonic glycerol (8 ml/kg/day) intramuscularly to both hind legs of the rats in all groups except the sham group. The sham group received intramuscular saline at 8 ml/kg/day, and distilled water was administered orally 1, 24, and 48 hours after saline administration. Food and water access was restricted 24 hours prior to glycerol and saline administration. The (glycerol) group received 3 ml/kg of distilled water orally 1, 24, and 48 hours after glycerol administration. Glycerol+KCS3 and Glycerol+KCS6 groups: In the short-term low-dose and high-dose treatment groups, glycerol was administered to the rats on the seventh day of the study. Oral gavage with hemp seed oil at a dose of 3 ml/kg/day to 6 ml/kg/day was administered 1, 24, and 48 hours after glycerol administration. In the Glycerol+UCS3 and Glycerol+UCS6 groups, hemp seed oil was administered orally via gavage at a dose of 3 ml/kg/day–6 ml/kg/day for 10 days. On the seventh day of the study, hemp seed oil administration at a dose of 3 ml/kg/day–6 ml/kg/day was continued 1, 24, and 48 hours after glycerol administration. After the first glycerol injection, the animals were allowed free access to food and water. Blood and tissue samples were collected 72 hours after glycerol administration, and the animals were sacrificed. In the sacrificed rats, renal function tests were performed on blood (BUN, creatinine) and renal tissue MDA, MPO, CAT, SOD, GSH, TNF-α, IL-1β, IL-6, HIF-1α, and caspase-3 biochemical parameters. In addition, the degree of renal damage was evaluated in the renal tissue histopathological evaluation. Results: In this study, the effects of oral administration of Cannabis sativa (hemp) seed oil at different doses and durations were evaluated in a glycerol-induced myoglobinuric acute kidney injury (MABH) model. Biochemical analysis revealed that creatinine, BUN, MDA, MPO, HIF-1α, caspase-3, TNF-α, IL-6, and IL-1β levels were significantly reduced in the treatment groups compared to the glycerol group, while GSH and CAT levels were increased (p<0.001). Histopathological examinations also revealed significant improvements in necrosis, congestion, mononuclear infiltration, and Bowman's capsule expansion in all treatment groups, with tissue samples from the glycerol+UCS6 group being the closest to those from the sham group. Conclusion: We can conclude that oral administration of hemp seed oil reverses the biochemical and histopathological findings of glycerol-induced acute kidney injury in rats, likely due to its antioxidant, anti-inflammatory, and anti-apoptotic properties. Based on the findings of our study, we believe that oral administration of hemp seed oil may also positively alter the biochemical and histopathological outcomes in a myoglobinuric acute kidney injury model in humans Keywords: Acute kidney injury, hemp seed oil, rhabdomyolysis, inflammation, antioxidant, apoptosis