Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney
BMC Pharmacology
Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney
Naveen Tirkey 0
Sangeeta Pilkhwal 0
Anurag Kuhad 0
Kanwaljit Chopra 0
0 Address: Pharmacology division, University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh-160014 , India
Background: CCl4 is a well-established hepatotoxin inducing liver injury by producing free radicals. Exposure to CCl4 also induces acute and chronic renal injuries. The present study was designed to establish the protective effect of hesperidin (HDN), a citrus bioflavonoid, on CCl4induced oxidative stress and resultant dysfunction of rat liver and kidney. Methods: Animals were pretreated with HDN (100 and 200 mg/kg orally) for one week and then challenged with CCl4 (2 ml/kg/s.c.) in olive oil. Rats were sacrificed by carotid bleeding under ether anesthesia. Liver enzymes, urea and creatinine were estimated in serum. Oxidative stress in liver and kidney tissue was estimated using Thiobarbituric acid reactive substances (TBARS), glutathione (GSH) content, superoxide dismutase(SOD), and Catalase (CAT) Results: CCl4 caused a marked rise in serum levels of ALT and AST (P < 0.05). TBARS levels were significantly increased whereas GSH, SOD and CAT levels decreased in the liver and kidney homogenates of CCl4 treated rats. HDN (200 mg/kg) successfully attenuated these effects of CCl4 Conclusion: In conclusion, our study demonstrated a protective effect of HDN in CCl4 induced oxidative stress in rat liver and kidney. This protective effect of HDN can be correlated to its direct antioxidant effect.
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Background
Drug exposure, ionizing radiations and environmental
pro-oxidant pollutants induce free radical formation.
Lipid peroxidation initiated by free radicals is considered
to be deleterious for cell membranes and has been
implicated in a number of pathological situations.
Carbontetrachloride (CCl4), an industrial solvent, is a
wellestablished hepatotoxin [1-3]. Various Studies
demonstrated that liver is not the only target organ of CCl4 and it
causes free radical generation in other tissues also such as
kidneys, heart, lung, testis, brain and blood [4-6]. It has
also been reported that exposure to CCl4 induces acute
and chronic renal injuries [7,8]. Case control studies and
various documented case reports increasingly establish
that hydrocarbon solvents produce renal diseases in
humans [9].
Extensive evidence demonstrates that as a result of the
metabolic activation of CCl4, CCl4 and Cl, are formed
which initiate lipid peroxidation process. Vitamin E
protected CCl4-induced liver injury indicating the role of
oxidative stress in this model [10]. Studies also show that
Bilirubin total (mg/dl)
Values are expressed as percent response compared to control rats. a = Statistical significant at P < 0.05 as compare to control, b = Statistical
significant at P < 0.05 as compare to CCl4, c = Statistical significant at P < 0.05 as compare to CCl4+ HDN(100)
certain natural extracts containing antioxidants protect
against the CCl4-induced increased lipid peroxide levels
and impairment in hepatic GSH status [11].
Hesperidin is a flavanone glycoside abundantly found in
sweet orange and lemon and is an inexpensive by-product
of citrus cultivation [12]. Hesperidin is effectively used as
a supplemental agent in the treatment protocols of
complementary settings. Its deficiency has been linked to
abnormal capillary leakiness as well as pain in the
extremities causing aches, weakness and night leg cramps.
Supplemental hesperidin also helps in reducing oedema or
excess swelling in the legs due to fluid accumulation. A
number of researchers have examined the antioxidant
activity and radical scavenging properties of hesperidin
using a variety of assay systems [13-16].
Thus the present study was designed to investigate the
effect of HDN on CCl4-induced oxidative stress and
resultant dysfunction of rat liver and kidney.
Results
Effect on liver enzymes
CCl4 caused a marked rise in serum levels of ALT (control
= 45 IU/L) and AST (control = 135 IU/L) demonstrating a
marked liver damage. Treatment with HDN decreases the
elevated levels of ALT and AST in serum (P < 0.05)(Table
1). Both the doses of HDN also attenuated the
CCl4induced elevated levels of total bilirubin (control = 0.184
mg/dl).
Effect on hepatic and renal TBARS levels
CCl4 challenge caused a marked lipid peroxidation in
both liver (control = 1.5 micromoles/mg protein) and
kidney (control = 33.86 nmoles/mg protein). Both the
doses of HDN decreased the level of lipid peroxidation in
liver, but in the kidney, no effect on lipid peroxidation
was seen with 100-mg/kg dose, and only the higher dose
of HDN (200 mg/kg) could attenuate the increased level
of lipid peroxidation (P < 0.05) (Fig 1). 7-day oral feeding
of HDN per se (200 mg/kg) did not result in a significant
alteration of either hepatic or renal TBARS levels.
Effect on the glutat (...truncated)