TOXICOPATHOLOGY OF CISPLATIN AND ITS AMELIORATION BY TURMERIC IN RATS
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Date
2011-10
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA
Abstract
ABSTRACT:
Cancer is one of the most dreadful diseases and currently taking the heaviest toll of human lives, with distant hope of finding an effective and complete cure unless detected and treated in early stages. Unfortunately till today no drug has been found as the master in treating cancer since most of the drugs are having little or lot of side affects. Cisplatin is one of the most remarkable successes in the war on cancer. The present study was aimed to evaluate the protective effect of turmeric in cisplatin induced toxicity in rats. A total of 48 rats which were divided into 4 groups and treated as follows: Group 1: control, 2: cisplatin control @ 2 mg/kg b.wt, 3: turmeric control @ 0.05 mg/kg b.wt and 4: cisplatin + turmeric each with the above mentioned doses.
Body weights were recorded at weekly intervals and organ weights were recorded at the time of sacrifice on day 28. Whole blood was collected for estimation of haematological parameters like RBC, Hb, WBC and PCV. Serum was separated for estimation of biochemical parameters like total protein, BUN, AST, GGT, CPK and creatinine. Studies on whole blood and serum were conducted at fortnightly interval. Visceral organs such as kidney, liver, brain, heart, stomach and intestines were collected for estimation of TBARS, GSH and protein carbonyls in tissue homogenates. Activity of SOD, catalase, G6PD, GPX, GSTNa+-K+ ATPase, Mg2+ATPase and CYP450 was estimated in liver. At the time of sacrifice gross pathological lesions were noted, tissue pieces from kidney, liver, brain, heart, stomach and intestine were collected and preserved in neutral buffered formalin for histo-pahology. Tissue pieces of kidney were also preserved in glutaraldehyde for transmission electron microscopy.
Body weight gain, relative organ weight, RBC, WBC, Hb, PCV, serum protein, GSH, SOD, catalase, GST, GPX, G6PD, Na+/K+ ATPase and Mg2+ATPase were significantly (P < 0.05) decreased in cisplatin administered group, while CYP450, TBARS, protein carbonyls, serum BUN, AST, GGT, CPK and creatinine were significantly (P < 0.05) increased in group 2. Group 1 and 3 did not reveal any significant abnormalities. The ameliorative group 4 showed mild to moderate improvement in all parameters in comparison to group 2.
Gross pathology of group 2 rats revealed reduction in size of kidney, shrunken liver with small abscess and moderate hemorrhages on lungs. Histopathological sections from kidney of group 2 rats showed marked intertubular hemorrhages, congestion, marked dilation of tubules, shrunken glomeruli and few with disappeared capillary network. Some sections showed hyaline casts, appreciable degenerative changes in tubular epithelium and mild fibrosis. Sections from liver showed marked central vein and sinusoidal congestion, bile duct hyperplasia, few hepatocytes with hydropic degeneration and other degenerative changes. Sections from brain revealed marked congestion of cerebral vessels, mild subcapsular hemorrh-ages, liquefactive necrosis, gliosis and perivascular cuffing. Sections from heart revealed marked interfibrillar congestion, hemorrhages in purkinjee fibres, disrupted cardiac muscle fibres and round cell infiltration. Sections of stomach showed marked congestion and hemorrhages between the villi and also at the base of villi, swollen villi with loss of epithelium at the tips and edematous fluid between villi. Sections from intestine showed marked disruption of villi epithelium.
The gross and histopathological lesions in group 4 were mild compared to group 2. Groups 1 and 3 did not reveal any lesions of pathological significance.
Ultrastrucural changes in rats of group 2 showed moderate dilation of tubules, varied shapes and sizes of mitochondria, disruption of nuclear chromatin material, perinuclear clumping of mitochondria, marked cytoplasmic vacuolation, margination of chromatin material, disrupted and condensed endoplasmic reticulum, nuclear changes like pyknosis, dilation of nuclear pores and condensation. Rats of group 4 showed nucleus with uniform size, well differentiated nuclear membrane and nucleolus, intact inner and outer nuclear membranes, regenerating mitochondria with prominent inter tubular and inter cellular junctions.
From this study, it was concluded that the adverse effects of cisplatin can be reverted by administration of turmeric in a dose-dependent manner.
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