STUDY OF PROTECTIVE EFFECTS OF ASCORBIC ACID AND SPIRULINA AGAINST TOXICOPATHOLOGY OF DOXORUBICIN IN RATS
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Date
2008-10
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA
Abstract
ABSTRACT:
Cancer is one of the major life threatening conditions in humans and animals. 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. Doxorubicin comes under antibiotic class of anticancerous drugs. An experiment was designed to evaluate Doxorubicin toxicity and its amelioration with ascorbic acid and Spirulina. A total of 24 healthy female Wistar rats (weighing 150-200g) procured for the present experimental study and the experiment was carried out according to the guidelines and prior approval of Animal Ethics Committee. Animals were divided into four groups consisting of 6 in each group. The experimental study was designed as follows: Group 1-Control, Group 2-Doxorubicin – Toxic control @ 2mg / kg body wt. by intravenous injection for 5 days followed by weekly once for 2 weeks, Group 3-Pre treatment with ascorbic acid @ 500mg / kg feed by enteral route for 7 days followed by intravenous injection of Doxorubicin as mentioned in group 2. Ascorbic acid supplementation was continued during these 19 days, Group 4-Pre treatment with Spirulina @ 1000mg / kg feed by enteral route for 7 days followed by intravenous injection of Doxorubicin as mentioned in group 2. Spirulina supplementation was continued during these 19days. But In group 2, 100% mortality was recorded on three days after 5th dose of doxorubicin and in group 3, 50% mortality was recorded. Hence, the experiment was terminated on day 8. Body weights were recorded on zero day and 6th day; Haematological and sero-biochemical parameters were estimated and analyzed statistically in the samples collected on 6th day. Day 1 is the day of administration of 1st dose of Doxorubicin. Body weights, heart weights and heart weight/body weight ratio were significantly (P<0.05) reduced in group 2 in comparison to other groups. Haematological studies revealed that overall means of TEC, Hb, TLC and PCV were significantly (P<0.05) reduced significantly (P<0.05) in group 2 in comparison to other groups. The biochemical assays showed a significant (P<0.05) increase in CPK, LDH, cTn, AST, ALT, Serum creatinine and BUN group 2. The tissue enzymes assays revealed a significant (P<0.05) increase in TBARS and significant (P<0.05) decrease of GSH and SOD activities in group 2. The ameliorative groups 3 and 4 showed mild to moderate improvement in all parameters in comparison to group 2. The gross pathological changes in the group 2 animals included yellowish discoloration of liver and kidney; moderate to severe congestion of heart, liver and kidney; haemorrhages in endocardium, streaks of haemorrhages in liver and petechiae in kidney.In group 2 the histopathological changes in heart revealed severe disruption, separation, degeneration, necrosis, fragmentation of muscle fibres with endocardial haemorrhages, edema, moderate focal infiltration of lymphocytes. Kidney revealed marked congestion, disrupted tubular and glomeruli architecture, shrunken / atrophied glomeruli, marked degenerative changes in tubules along with marked intertubular haemorrhages and casts. Liver revealed marked central vein and sinusoidal congestion, bile duct hyperplasia, focal areas of necrosis, karyorrhexis and marked fatty changes. Group 3 and 4 animals heart revealed moderate range of interfibrillar haemorrhages, degeneration and disruption of muscle bundles. Kidney showed mild to moderate degenerative changes. Liver revealed mild to moderate central vein, sinusoidal congestion, dilatation of sinusoidal spaces degenerative changes in the hepatocytes.
The present study was concluded as follows:
1. The deleterious changes caused by doxorubicin in terms of performance and
haematology can be attributed to cardiac, kidney and hepatic damage .
2. The serobiochemical changes might be attributed to the toxic metabolites of doxorubicin
resulting in cellular damage.
3. The gross and the histological changes in the study might be due to the toxic reactive
metabolites of the drug which binds to cellular macromolecules and release or form toxic free radicals inturn cause the tissue damage.
4. Supplementation of vitamin C (0.5%) resulted in only slight improvement in the
haematological and biochemical parameters which can be attributed to the antioxidant effects.
5. Supplementation of Spirulina (1%) resulted in significant improvement in
performance, haematological and biochemical parameters that can be attributed to
the antioxidant, antistress and anti-inflammatory agent.
The present study indicated that vitamin C @500mg/kg feed was found to be less protective affective and Spirulina @ 1000mg/kg feed offered moderate protection in counteracting the toxic affects of Doxorubicin. Keeping this in view, further studies can be advocated using different doses and different routes of administration so as to obtain best results combating the affects of anthracycline drugs which would prove beneficial for animals and humans.
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