2
1
2021
1682060070609_2969
45-49
https://journal.smdc.edu.pk/index.php/journal/article/download/15/9
https://journal.smdc.edu.pk/index.php/journal/article/view/15
INTRODUCTION
Ibuprofen, classified as non-steroidal anti- inflammatory drugs (NSAIDs), was discovered by Dr. Stewart Adams in 1961 in Nottingham UK at the Boots Company laboratories. It is a one of the frequently administered medicines and is extensively available over the counter as well1, 2. It is generally used against fever, to relieve pain and an agent to eliminate inflammation. The greatest advantage of this medication is discovered to be
particularly helpful in the remedy of joint inflammation and other musculoskeletal con- ditions. Ibuprofen is likewise much of the time the medication of choice for alleviation of dental agony, headache, dysmenorrhea, flu and cold2.
Various results influencing different viscera are related with long term utilization of ibuprofen. The drug, therefore, has been related to cause a number of nephrotoxic effects resulting in damage to renal architecture, thus increasing the risk of renal failure. In other organ systems, ibuprofen has been found to cause gastric and duodenal ulcers, hepatitis and cardiac failure3. The neph-rotoxic effects of ibuprofen mainly result from the oxidative damage to renal tissue caused by rea- ctive oxygen species which are generated during the metabolism of the drug4.
The kidney is actively involved in the bio- transformation of different medications and is thus widely exposed to their unfavorable side-effects. The degenerative effects of NSAIDs, especially ibuprofen on kidneys have been reported and well- accepted5.
Green tea (Camellia sinensis) is quite possibly the most well-known, profoundly devoured drinks all throughout the planet. It has been found to be a powerful nephron protective specialist against the unhealthy effects of various medications. Green tea contains polyphenols; mostly flavonoids amo-ng which 80-90% are catechins. The green tea catechins have strong antioxidant properties6 and defends the renal tissue against oxidative stress, hence forestalling the harm brought about by reactive oxygen species generated from ibuprofen biotransformation7.
In addition to its nephron-protective properties, green tea has long been believed to have beneficial effects on cardiovascular and gastro-intestinal systems. To date, antibacterial, antiviral, anti- inflammatory, anticancer and anti-hypertensive benefits of the constituents of the green tea have
been observed8. Knowledge of the beneficial effect may highlight its significance for clinical utilization as a part of treatment regime which could be best assessed by renal function tests.
MATERIALS AND METHODS
This laboratory based experimental study was conducted at the Anatomy Department, Army Medical College Rawalpindi, for duration of one year. The study was performed following the approval of ethical committee on animal exper- iments, of Army Medical College, Rawalpindi.
Thirty (30) adult male healthy rats along with non- pregnant female Sprague Dawley rats of 9- 11 weeks of age and weights ranging from 200-330 gm were used in the experiment and were acclimatized in the animal house of National Institute of Health (NIH), Islamabad. Rats were segregated into three groups (n=10 in each group) where male rats were kept in isolated confines from the females. Rats were fed NIH standardized lab diet for sixty days and water was supplied ad libitum. Ibuprofen manufactured by Abbot Laboratories (Pvt.) Limited was utilized. Green tea was obtained from local market. At the end of 9 weeks but 24h after administration of last dose, five milliliters of blood were taken through intracardiac route and collected in labeled vials. The samples were sent to Pathology Laboratories, Army Medical College for biochemical analysis of serum urea and creatinine (Table 1).
Statistical Analysis
The data was analyzed using statistical package for social sciences (SPSS version 22). The biochemical parameters were narrated as mean ± standard deviation and the critical contrast was resolved utilizing analysis of variance (ANOVA), after which Post-hoc Tukey test. Results were believed significant at p value of <0.05.
Table 1: Experimental Grouping of Animals, Mode of Intervention and Dosage of Drugs |
||||
Groups |
Intervention& Dosages |
Number of Administrations (per day) |
Route of Administration |
Duration of Administration (weeks) |
A |
Distilled water & NIH lab diet |
Once |
Orally by gavage tube |
9 |
B |
Ibuprofen (120mg/kg body weight) |
Once |
Orally by gavage tube |
9 |
C |
|
Once |
Orally by gavage tube |
9 |
Table 2: Mean Values of Biochemical Analysis of Control Group A, Interventional Groups (B and C) and Intergroup Comparison of p-values (n = 10) |
||||||
Parameters |
Group A (Mean ± SD) |
Group B (Mean ± SD) |
Group C (Mean ± SD) |
Group A vs. B |
Group A vs. C |
Group B vs. C |
Serum urea (mg/dl) |
21.9 ± 2.8 |
93.2 ± 3.9 |
36.4± 3.0 |
0.000 |
0.000 |
0.000 |
Serum creatinine (mg/dl) |
0.9 ± 0.22 |
2.4± 0.52 |
0.97 ± 0.3 |
0.000 |
0.819 |
0.000 |
RESULTS
The serum levels of urea and creatinine after ibuprofen administration were generally higher in the experimental group B when compared to control group A. The biochemical markers clear- ance levels in tea given group C were found to be lower when compared to the other experimental group.
For serum urea, significant disparity in statistical terms was seen among all the groups (Figure 1). For serum creatinine, statistically substantial distinction was noticed between control group A and experimental group B but not between control group A and experimental group C. The comp- arison between experimental groups B and C, nevertheless, revealed a statistically significant difference (Table 2, Figure 1 and 2).
DISCUSSION
Kidney is an exceedingly active organ involved in metabolism and is accountable for the metabolism of a vast range of chemicals and drugs. In metabolic terms, the reactive intermediates consequence of the metabolic conversion of most of the drugs cause the nephrotoxic effects9. Ibuprofen is utilized for the therapy of pyrexia, dental & post-operative pain, dysmenorrhea, migraine, rheumatoid and osteoarthritis, disorders of the soft tissue and various inflammatory dis-orders on a vast scale10.
The detrimental effect of Ibuprofen on renal tissue is well-documented and is mostly consequence of its potential to generate the quantity of reactive oxygen species which subsequently lead to the per oxidative reaction damaging the renal tissue. These
Figure 1: Bar charts illustrating the correlation of mean values of serum urea in control group A and interventional groups B and C
Figure 2: Bar charts illustrating the comparison of mean values of serum creatinine in control group A and experimental groups B and C
incorporate renal failure and interstitial nephritis on acute basis, tubular necrosis, acute necrosis, and quickened chronic renal failure11.
Green tea, primarily by quality of its preventive activity against oxidative stress, has strong protective effects on renal tissue. It protects against glomerulosclerosis and reduces serum creatinine and urea11. The tea was also ascribed to have a shielding impact not in favor of injury to the renal ischemia and renal tubules triggered by cyclosporine A12. Biochemical parameters including serum urea and creatinine, were evaluated for all rodents in all groups. The levels of urea and creatinine in the serum came out elevated significantly in experimental group B when compared to control A. Abbas and Abed proven that ibuprofen elevated urea and creatinine in the serum on significant terms13. These two parameters are key markers of intense kidney injury, particularly in youngsters. Subsequently, ibuprofen instigated intense kidney infection in youngsters will in general be more extreme and set aside more effort to recuperate than in grown-ups14. An investigation directed on Holstein calves showed expanded serum urea and creatinine following 10- day ibuprofen administration15. An investigation
comparing acetaminophen vs ibuprofen performed on rabbits by revealed that ibuprofen raised up levels of urea and creatinine more compared with the latter, employed as an alternative16. Elevated values of blood-urea and creatinine depict substantial renal damage and are credited to oxidative stress caused by reactive oxygen species generated from the metabolism of the ibuprofen. Green tea administration in experimental group C brought about huge betterment of serum urea and creatinine levels when contrasted with group B. Consequently, action of green tea polyphenols against oxidation is liable for keeping up these markers of renal operation inside typical cutoff points.
CONCLUSION
Green tea had ameliorative effects on the ibuprofen-induced changes in the biochemical markers of the adult rat kidneys.
Acknowledgements
We are grateful to the staff of National Institute of Health for all of their support and facilitation.
Conflicts of interest
The authors declare that they have no conflict of interests.
Contributors
Dr. Afnan Gul contributed to concept, design of the study& data collection. Drafting & data analysis was done by Dr. Muhammad Bahadur Baloch. Dr. Afnan Gul critically revised the article and approved the final version.
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Abireh IE, Ozioko OM, Ozor II, Finbarrs-Bello E, Ozioko US, Egbo F. Azadirachta indica (neem) leaf extract effect as an option of treatment of ibuprofen- induced nephrotoxicity. J Adv Med Med Res. 2020; 25: 56-62.
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Nadimohamed N, Mahmoud B, Abdel-Reheim ES, Abdel-Moneim A. Olive and basil leave extracts protect against Ibuprofen induced nephrotoxicity in albino rats. Res J Pharm Technol. 2020; 13(9): 4190- 4.
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