Indian Journal of Experimental Biology Vol. 42, August 2004, pp. 766-769

Quercetin attenuates thermal and cold in STZ-induced diabetic rats

Muragundla Anjaneyulu & Kanwaljit Chopra* Pharmacology Division, Universit y In stitute of Pharmaceutical Sciences, Panjab University, Chandigarh , I 60 014, India

Received 21 January 2004; revised 5 May 2004

Neuropathic is one of the important mi crovascular complications of diabetes. Oxidative stress and superoxide play a criti cal role in th e development of neurovascular complications in diabetes. Aim of th e present study was to eva lu ate the effec t of qu ercetin, a bi onavo noid on thermal nocicepti ve responses in streptozotoci n (STZ)-induced diabetic rats assessed by tail-immersion and hot plate meth ods. After 4-weeks of a single intra venous STZ injecti on (45 mg/kg body wei ght), diabetic rat s exhibited a significant th ermal hyperal gesia and cold all odynia along with in creased plasma glucose and decreased body weights as compared with control rat s. Chronic treatment with quercetin (I 0 mg/kg body wei ght; p.o) for 4- weeks starting from the 4' 11 week of STZ-injection significantly attenuated th e cold all odyni a as well as hypera lges ia. Results indicate th at qu ercetin, a natural anti ox idant, may be helpful in diabetic neuropathy.

Keywords: Diabeti c neuropathy, Hyperalgesia, Quercetin, Cold all odyni a, Tail-immersion, Hot plate.

Neuropathic pain is one of the most common Based on and antioxidant properties of complications in diabetes mellitus. Jt is mostly quercetin, the present study has been aimed to characteri zed by hyperalgesia and allodynia. Clinical evaluate the effect of quercetm on thermal and experimental studies have revealed that reactive hyperalgesia and cold allodynia, the indices of oxygen species (ROS) play a significant role in diabetic neuropathic pain in rats. pathophysiology of neuropathic pain in diabetes. Materials and Methods Quercetin (3, 5, 7, 3', 4'-pentahydroxyflavone) is a Animals-Male Sprague-Dawley rats (200-250 g) phenolic compound widely distributed in the plant bred in Central Animal House facilities of Panjab kingdom. [t is found in many frequently consumed University were housed under optimal laboratory foods, including apples, onion, tea, berries and conditions. Animals were acclimatized to laboratory brassica vegetables. Renewed interest has been conditions before the experiments th at were carried observed in recent years on multipk activities of out between 0900 and 1700 hr. Approval of novel bioflavonoids. They are reported t•) have many Institutional Animal Ethics Committee was obtained. beneficial effects on human health, including Treatment schedule-After a basal reading at 4'h cardiovascular protection, anticancer activity, anti­ week of STZ injection, control and diabetic rats were ulcer effects, anti-allergic activity, cataract randomly selected and divided in three groups of 6-7 prevention, antiviral activity and anti-inflammatory 2 animals each. i.e. control, diabetic control and effects I. . There are sporadic reports on the analgesic diabetic group treated with quercetin. Starting from activity of certain flavonoids such as hydroxy ethyl 3 4 the 4'" week till 8'" week, the control and diabetic rutoside and gossypin . Recently it has been reported 5 control groups received vehicle of quercetin and that quercetin has analgesic activity in naive animals 6 another diabetic treated group received suspension of tested in few test systems . Moreover, quercetin has quercetin (10 mg/kg body weight/day) orally. been reported to inhibit oxidative damage in various 7 Quercetin (Sigma Chemical, St.Lo ... is , MO, USA) tissues of STZ-induced diabetic rats . suspension was prepared in 0.5 % carboxy methyl cell ulose solution. All the drugs were administered in *Corresponden t author a constant volume of 0.5 mil I OOg body weight of rat. Ph one: 0172-2534105 Fax: +91 -172-2541 142 Induction and assessmellt of diabetes-A single E- mail : · ·r [email protected] dose of 45-mg/kg body weight STZ (Sigma Chemical, ANJANEYULU & CHOPRA: DIABETIC PAIN & QUERCETIN 767

St.Louis, MO, USA) prepared in citrate buffer (pH tests-At the end of 4th week, diabetic animals 8 4.4, 0.1 M) was injected through tail vein . The age exhibited significant decrease in pain threshold from matched control rats received citrate buffer and used noxious stimuli as compared to control rats along with diabetic animals. Diabetes was confirmed (P

Ill Control DDiabetes 0 Diabetes+Quercetin 14 b b 12 ® 10 8 6 4 2 0 u 15 II) ..!!!.. II) 10 E ; c: 0 ; 5 0 Ill II) 0:: 0 5 4 3 2 1 0 0 1 2 3 4 Treabnent (week)

Fig. !-Effect of chronic treatment of quercetin on pain threshold values in STZ-injected diabetic rats subjected to the tail immersion test in (A) hot water (47° ± I °C), (B) cold water (10° ± 0.5 °C) and (C) the hot plate test (55° ± I °C). [Values are in mean± S.E. P values; •<0.00 I as compared with control rats at before and respective week; b

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