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The role of Δ9-Thc on oxidative stress status of brain and cerebellum in type-2 diabetes

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THE ROLE OF Δ

9

-THC ON OXIDATIVE STRESS STATUS OF

BRAIN AND CEREBELLUM IN TYPE-2 DIABETES

5th THE INTERNATIONAL CONGRESS ON CELL MEMBRANES AND OXIDATIVE STRESS: FOCUS ON CALCIUM

SIGNALING AND TRP CHANNELS, 9 - 12 SEPTEMBER 2014, ISPARTA-TURKEY

ZEYNEP MINE COSKUNa, SEMA BOLKENTb

aDepartment of Molecular Biology and Genetics, Faculty of Arts and Sciences, Istanbul Bilim University, Istanbul, Turkey bDepartment of Medical Biology, Faculty of Cerrahpasa Medicine, Istanbul University, Istanbul, Turkey

INTRODUCTION

MATERIAL AND METHOD

RESULTS

REFERENCES

[1] Ceretta LB et al. Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. Exp Diabetes Res. 2012;2012:302682.[2] Shinde SN et al. Evaluation of oxidative stress in type 2 diabetes mellitus and follow-up along with vitamin E supplementation. Indian J Clin Biochem 2011; 26: 74-77. [3] Chen J et al. Reactive oxygen species and p38 phosphorylation regulate the protective effect of delta9-tetrahydrocannabinol in the apoptotic response to NMDA. Neurosci Lett 2005; 389: 99-103. [4] Moldzio R et al. Effects of cannabinoids tetrahydrocannabinol, Δ(9)-tetrahydrocannabinolic acid and cannabidiol in MPP+ affected murine mesencephalic cultures. Phytomedicine 2012; 19: 819-824. [5] Sagredo O et al. Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease. J Neurosci Res 2011; 89: 1509-1518.

8-10 week-old Sprague-Dawley rats were divided into 4 groups. Group I: Physiological saline was administered intraperitoneally (i.p) (n=7). Group II: Rats

that are given Δ9-THC for 7 days (3 mg/kg/day) (n=6)

(i.p). Group III: Streptozotocin (STZ, 65 mg/kg) +Nicotinamide (NAD, 85 mg/kg) (n=7) (i.p). Group IV:

Diabetic rats that are given Δ9-THC (3 mg/kg/day) for 7

days (n=7) (i.p). Malondialdehyde (MDA) and reduced glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities were measured in brain and cerebellum tissue samples of rats.

Diabetes Mellitus is a metabolic disorder characterized by hyperglycemia. The hyperglycemia leads to neuronal damage [1]. The development and progression of diabetes mellitus and its complications are derived from increased oxidative damage [2]. Many

studies report that Δ9-THC is protective for neuronal

injury in experimental models and exhibits anti-oxidative action [3-5].

In this study, we aimed to explore the curative effect

on oxidative stress of Δ9THC in the brain and

cerebellum of type-2 diabetic rats.

The results showed that GSH levels of the brain and cerebellum were non-significantly decreased in the diabetic rats as compared with the control group. The GSH levels of the brain and cerebellum were non-significantly

increased in the diabetes+Δ9-THC group when compared with the diabetic group. It was found that the increased

MDA levels of the brain and cerebellum in diabetic rats were decreased by treatment with Δ9-THC. In the diabetic rats

treated with Δ9-THC, the SOD activities of the brain and cerebellum were elevated as compared with diabetes group.

The brain and cerebellum CAT activities were non-significantly increased in the diabetic rats treated with Δ9-THC, as

compared with the diabetes group.

CONCLUSION

In conclusion, it is suggested that Δ

9

-THC has curative effects against oxidative stress in type-2 diabetic

rats. Δ

9

-THC may be conferred in diabetes treatment with an appropriate dose due to its antioxidant effects.

*Mean ± Standart Error of Mean (SEM), NS: Non-significant

aP<0.01 versus control group; bP<0.05 versus control group; cP<0.01 versus Δ9-THC group; dP<0.01 versus diabetes group; eP<0.05 versus diabetes group

Table: Biochemical parameters in all groups

BRAİN CEREBELLUM Groups GSH* (nmol/mg) MDA* (nmol/mg) SOD* (U/mg) CAT* (U/mg) GSH* (nmol/mg) MDA* (nmol/mg) SOD* (U/mg) CAT* (U/mg) Control (n=7) 50.09 ± 3.07 4.07 ± 0.37 4.16 ± 0.36 9.53 ± 1.16 48.49 ± 4.29 3.69 ± 0.33 7.29 ± 0.38 11.82 ± 0.50 Δ9-THC (n=6) 63.59 ± 9.50 6.41 ± 0.92b 6.05 ± 0.93 10.12 ± 2.01 38.47 ± 4.53 3.51 ± 0.35 5.52 ± 0.58b 7.55 ± 1.16 Diabetes (n=7) 48.06 ± 2.86 6.47 ± 0.80a 4.56 ± 0.35 8.54 ± 1.06 39.78 ± 3.47 4.96 ± 0.21a,c 5.45 ± 0.56a 8.84 ± 1.21 Diabetes + Δ9-THC (n=7) 62.27 ± 9.53 5.45 ± 1.50 5.24 ± 0.69 9.12 ± 1.31 45.47 ± 3.03 3.74 ± 0.33d 6.86 ± 0.51e 8.98 ± 1.65 PANOVA NS NS NS NS NS P<0.05 NS P<0.05

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