EFFECTS OF LYCOPENE ON BLOOD GLUCOSE AND PHYSIOLOGICAL PARAMETERS OF STREPTOZOTOCIN-INDUCED DIABETIC WISTAR RATS

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Department of Medicine

ABSTRACT
Diabetes mellitus is a major health problem in the world and is diagnosed by the presence of sustained high glucose levels in the blood. Oxidative stress is known to be actively involved in the onset and progression of diabetes and its complications. Antioxidants have important roles in biological systems by scavenging free radicals which may result in oxidative damage of biological molecules such as lipids, proteins and DNA. The aim of the study was to investigate the effects of lycopene on blood glucose level and some physiological parameters of streptozotocin-induced hyperglycaemic Wistar rats as model. The animals were made diabetic by single intraperitoneal injection of STZ (60 mg/kg). Diabetes was confirmed by the presence of high blood glucose ≥ 200 after 72 hours. Thirty Wistar rats of both sexes were used in the study of which twenty five of them were diabetic. They were divided into six groups (1, 2, 3, 4, 5 and 6) comprising five animals each. Animals in Group 1 (Diabetic control) and Group 2 (Normal control) received 0.5 ml of live oil while those in groups 2, 3, 4, 5 and 6 were administered 10, 20, 40 and 2 mg/kg b w of lycopene and glibenclamide respectively orally once daily for a period of four weeks. At the end of the treatment, all animals were sacrificed; blood samples collected and the serum separated for determination of biochemical and physiological parameters. The liver and kidney tissues were excised and subjected to routine histological investigation for hepatic glycogen alteration and histo-pathological changes. The results showed that lycopene at all doses significantly (P < 0.05) decreased the blood glucose concentration from (431.4 ± 48.84 mg/dL) to (171.1 ± 7.65, 118.4 ± 1.97 and 100.8 ± 6.89 mg/dL) after four weeks of treatment. The Serum insulin level was increased from (3.02 ± 0.24 μIU/mL) to (4.02 ± 0.70, 3.96 ± 1.41 and 5.06 ± 0.96 μIU/mL) but however, was not significant (P < 0.05), while the activity of hepatic glucokinase was significantly (P < 0.05) increased in diabetic animals from (8.78 ± 1.11 ng/mL) to (11.96 ± 0.54, 14.23 ± 0.88 and 15.78 ± 0.27 ng/mL) when compared with diabetic control group. The hepatic glycogen content was significantly (P < 0.05) elevated from (4.10 ± 0.09 mg/g tissue) to (6.00 ± 0.18, 6.28 ± 0.19, 7.18 ± 0.17 mg/g tissue) as reflected by significantly (P < 0.05) dose dependent increase in percentage hepatic glycogen levels (44.40 ± 4.81, 53.61 ± 6.63, 78.24 ± 4.88 %). Histological observation also revealed improvement on hepatic glycogen stores. There was significantly (P < 0.05) decreased activities of serum liver enzymes from (91.20 ± 2.06 IU/L) to (47.40 ± 1.81, 38.20 ± 0.86 and 36.20 ± 0.86 IU/L) for vii AST, (93.60 ± 3.25 IU/L) to (51.00 ± 1.73, 40.80 ± 1.59 and 39.00 ± 3.15 IU/L) for ALT and (134.80 ± 3.14 IU/L) to (78.40 ± 2.38, 59.20 ± 7.33 and 72.80 ± 2.65 IU/L) for ALP. The serum levels of TC, TRIG and LDL-c in diabetic rats were significantly (P < 0.05) reduced to (2.30 ± 0.09 and 2.30 ± 0.08 mmol/L), (1.00 ± 0.07, 0.72 ± 0.06 and 0.52 ± 0.04 mmol/L) and (1.16 ± 0.06, 0.89 ± 0.20 0.53 ± 0.22 and 1.11 ± 0.05 mmol/L) while the HDL-c level was improved to (1.18 ± 0.05, 1.26 ± 0.16 and 1.44 ± 0.17 mmol/L) when compared with diabetic control group. The atherogenic risk predictor indices (LDL-cholesterol/HDL-cholesterol), log (TRIG/HDL-cholesterol) and (CRR) (TC/HDL-cholesterol) were significantly (P < 0.05) decreased to (1.00 ± 0.10, 0.81 ± 0.22, 0.45 ± 0.21 mmol/L), (0.89 ± 0.09, 0.62 ± 0.11, 0.39 ± 0.07 mmol/L) and (2.17 ± 0.11, 1.94 ± 0.24 and 1.70 ± 0.23 mmol/L), while (HDL-cholesterol/TC) was significantly ( P < 0.05) elevated to (0.46 ± 0.02, 0.56 ± 0.08, 0.63 ± 0.09 mmol/L) when compared with diabetic control group. There was a corresponding increased percentage protections of (31.75 ± 7.05, 37.97 ± 9.11, 44.04 ± 9.92 %) in diabetic animals. Serum cortisol and MDA levels were significantly (P < 0.05) reduced to (5.36 ± 0.45, 6.42 ± 0.48 and 8.86 ± 0.44 μg/dL) and (2.22 ± 0.07, 1.76 ± 0.20, 1.52 ± 0.19 μg/dL) while there was up-regulated activities of serum endogenous enzymes: SOD to (1.90 ± 0.05, 2.14 ± 0.09, 2.40 ± 0.14 nmol/ml), CAT to (46.60 ± 1.503, 50.40 ± 1.75, 55.20 ± 1.43 nmol/ml) and GSH-Px to (40.00 ± 2.09, 43.80 ± 2.04 and 47.60 ± 0.68 nmol/ml) in diabetic treated animals when compared with diabetic control group. There was significantly (P < 0.05) elevation of serum total protein, albumin and globulin levels to (65.80 ± 1.28, 65.60 ± 1.33, 66.80 ± 1.39 g/L), (37.80 ± 1.39, 36.00 ± 1.58, 38.20 ± 1.39 g/L) and (28.00 ± 0.32, 29.60 ± 1.03, 27.60 ± 0.51 g/L). However, albumin/globulin ratio was significantly (P < 0.05) reduced to (1.35 ± 0.06, 1.23 ± 0.08, 1.39 ± 0.06 g/L) and (1.37 ± 0.35 g/L) in diabetic treated rats when compared with diabetic control group. There was a significant (P < 0.05) increase of (138.80 ± 0.97, 135.20 ± 3.93 and 130.40 ± 4.69 mmol/L) in the serum sodium ion level and reduction of (3.14 ± 0.12, 2.20 ± 0.31 and 2.40 ± 0.18 mmol/L) in the serum urea level. There was significantly (P < 0.05) lowered erythrocytes MDA concentration to (1.48 ± 0.07, 1.26 ± 0.08, 1.02 ± 0.09 μmol/g Hb) in diabetic treated groups. At 0.5, 0.7 and 0.9 % Nacl concentrations, a significantly (P < 0.05) lowered erythrocyte osmotic fragility of (12.20 ± 0.66, 8.80 ± 0.37, 8.40 ± 0.75 and 10.6 ± 1.25 %), (3.00 ± 0.45, 2.00 ± 0.32, 1.60 ± 0.25 and 3.40 ± 0.75 %) and (1.60 ± 0.25, 1.80 ± 0.49, 1.40 ± 0.25 and 1.40 ± 0.25 %) were produced in diabetic treated animals when compared with diabetic control group. There were significantly (P < 0.05) elevated Hb concentration to (12.56 ± 0.32, 12.68 ± 0.36, 13.30 ± 0.35 g/dL) and (11.52 ± 0.51 g/dL), RBC (6.65 ± 0.28, 6.88 ± 0.31, 6.77 ± 0 .26) and (5.77 ± 0.29), PCV (35.62 ± 0.83, 35.84 ± 1.10, 37.46 ± 1.03 %) and (37.14 ± 2.80 %). In addition, MCV (53.92 ± 2.15, 55.82 ± 4.09, 64.58 ± 3.51 fl) and (61.64 ± 2.48 fl), MCH (18.90 ± 0.48, 18.96 ± 0.52, 19.78 ± 0.35 Pg) and (18.84 ± 0.21 Pg) and MCHC (33.09 ± 0.13, 34.64 ± 0.25, 36.42 ± 1.59 g/dL) and (34.06 ± 0.63 g/dL) were significantly (P < 0.05) higher in diabetic lycopene when compared DC group. There was a significantly (P < 0.05) increased Total WBC count from (6.70 ± 0.26) to (13.12 ± 1.65, 11.08 ± 1.58, 10.88 ± 0.59) and (10.72 ± 1.14), lymphocytes count from (4.26 ± 0.27) to (8.08 ± 0.69, 7.64 ± 1.33, 7.54 ± 0.53) and (7.92 ± 1.21) and neutrophils count from (1.50 ± 0.23) to (2.09 ± 0.10, 2.42 ± 0.34, 2.40 ± 0.16) and (2.30 ± 0.29) when compared with diabetic control group. Conversely, treatment of diabetic animals with lycopene and glibenclamide produced a significantly (P < 0.05) decreased neutrophli/lymphocyte ratio from (0.50 ± 0.04) to (0.32 ± 0.04, 0.28 ± 0.03, 0.32 ± 0.02) and (0.22 ± 0.03) and platelets counts from (892.60 ± 20.10) to (483.00 ± 52.92, 568.80 ± 80.20, 586.20 ± 40.65) and (509.20 ± 58.14) when compared with diabetic control group. In conclusion lycopene ameliorated the physiological and biochemical alterations in STZ-induced diabetic Wistar rats.