Hepatoprotective activity of raspberry ketone against streptozotocin-induced type 2 diabetes in male rats

Abstract

Type 1 diabetes encompasses a spectrum of metabolic disorders marked by insulin deficiency, resulting in elevated blood glucose levels, commonly referred to as hyperglycemia. This persistent condition often precipitates lipid profile abnormalities, causing cholesterol alterations, low-and high-density lipoproteins, and triglycerides. The liver is particularly vulnerable to increased oxidative stress and inflammatory responses, which activate the transcription of pro-apoptotic genes and ultimately contribute to hepatocyte damage. This study analyzed the potential therapeutic role of raspberry ketone (RK), a natural antioxidant with antiapoptotic and anti-inflammatory properties, in male albino rats with induced type 2 diabetes. Fifty rats were equally divided into five groups: control, rats orally administered 200 mg /kg Body Weight (BW) RK for 5 days, diabetic rats intramuscularly injected once with 60 mg/kg BW streptozotocin, streptozotocin-induced diabetic rats orally administered 200 mg/kg BW RK for 5 days, and streptozotocin-induced diabetic rats orally administered 100 mg/kg metformin. Streptozotocin treatment significantly affected blood biochemical parameters, lipid profiles, oxidative stress markers, immunotoxicity biomarkers, and DNA damage biomarkers. Conversely, RK efficiently ameliorated the toxic effects of streptozotocin on the liver by reducing the pathological and biochemical changes associated with diabetes through its antioxidant and anti-inflammatory properties. Therefore, incorporating RK into the diet of diabetic patients can help prevent hepatocyte damage associated with diabetes. In conclusion, oral administration of RK exerts hepatoprotective effects by offering antioxidant, antiapoptotic, and anti-inflammatory properties against streptozotocin-induced type 1 diabetes in male rats.

Fig 1. Effects of raspberry ketone and metformin- on blood glucose (mmol/L) levels on the day of dissection in control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 2. Effects of raspberry ketone and metformin on alanine aminotransferase (U/L) levels in control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 3. Effects of Raspberry ketones and metformin on aspartate aminotransferase (U/L) levels in control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 4. Effects of raspberry ketone and metformin on malondialdehyde (U/g) levels in the livers of control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 5. Effects of raspberry ketone and metformin on reduced glutathione (nmol/g) levels in the livers of control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 6. Effects of raspberry ketone or metformin on catalase (U/g) levels in the livers of control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 7. Effects of raspberry ketone and metformin on superoxide dismutase (U/mL) activity levels in the livers of control and experimental rats.

Similar superscripts indicate non-significant difference; different superscripts indicate significant difference.

Fig 8. DNA fragmentation in control and experimental rats.

Lane 1: control group; lane 2: rats treated with only raspberry ketone (RK) for 1 h; lane 3: rats treated with only raspberry ketone (RK) for 24 h; lane 4: diabetic group (50 mg/kg); lane 5: diabetic rats treated with metformin (50 mg/kg) for 1 h; lane 6: diabetic rats treated with metformin (50 mg/kg) for 24 h; lane 7: diabetic group treated with RK (200 mg/kg BW) for 1 h; lane 8: diabetic rats treated with RK (200 mg/kg BW) for 24 h.

Fig 9. Photomicrographs of rats’ livers.

(A) untreated control rats, (B) livers of rats treated with only raspberry ketone (RK) for 1 h, (C) livers of rats treated with only RK for 24 h (hematoxylin and eosin, 400×).

Fig 10. Photomicrographs of rat livers.

(D) diabetic rats showing dilated vein congested with edema (E) and surrounded with inflammatory cells (black arrow), (E) diabetic rats treated with raspberry ketone (RK) for 1 h revealing congested vein with edema (E), cytoplasmic degeneration (red arrow), swelling nucleus (blue arrow), (F) diabetic rats treated with RK for 24 h displaying cytoplasmic degeneration (red arrow), binucleated cell (black arrow), (G) diabetic rats treated with metformin for 1 h revealing cytoplasmic degeneration (red arrow), infiltrative cells (blue arrow), (H) diabetic rats treated with metformin for 24 h showing congested vein with edema (E), healthy hepatocytes (hematoxylin and eosin, 400×).

Fig 11. Photomicrographs of rat livers stained immunohistochemically against p53 showing weak immune response.

(A) untreated control rats, (B) rats treated with only raspberry ketone (RK) for 1 h, and (C) rats treated with only RK for 24 h (ABC, 400×).

Fig 12. Photomicrographs of rat livers stained immunohistochemically against p53.

(D) untreated diabetic rats showing strong immune response, (E) diabetic rats treated with raspberry ketone (RK) for 1 h, (F) diabetic rats treated with RK for 24 h, (G) diabetic rats treated with metformin for 1 h, and (H) diabetic rats treated with metformin for 24 h (D-H, 400×).