Evaluation of histo-toxicity of nimesulide in Black Kites (<i>Milvus migrans</i>): a pharmacodynamic study

Farooq, M.; Khan, A. A.

doi:10.1590/1519-6984.271454

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Brazilian Journal of Biology

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Original Article • Braz. J. Biol. 83 • 2023 • https://doi.org/10.1590/1519-6984.271454 copy

Evaluation of histo-toxicity of nimesulide in Black Kites (Milvus migrans): a pharmacodynamic study

Avaliação da histotoxicidade da Nimesulida em Milhafre-preto (Milvus migrans): um estudo farmacodinâmico

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

The present experimental work was conducted to elucidate the toxicity of nimesulide at three different doses in black kites (Milvus migrans). M. migrans is one of the most common raptors near human habitations. The goal of the current investigation was to determine whether nimesulide is similarly hazardous to raptors as was diclofenac sodium and to investigate the acute oral toxicity of nimesulide in these birds. For this study, eight adult male black kites (M. migrans) were randomly divided into four groups. M. migrans in the control group (n = 02) were not treated with nimesulide. The other three groups were given nimesulide doses. The birds in the first (n = 02) were declared the control group. The second (n = 02), third (n = 02), and fourth groups were administered nimesulide at a low, medium, and high dose of 2, 4, and 6 mg/kg live body weight of bird/day, respectively, for 10 days. Nimesulide-addled birds became listless and despondent, then anorexic. The birds were standing there with their eyes closed and showing no signs of life. There was an increase in saliva production, a slowing of breathing, and dilated pupils. No clinical signs were observed in the control group. No mortality was seen in the control or treated groups. The control group did not show lesions of gout, but black kites intoxicated with nimesulide at 2, 4, and 6 mg/kg live body weight of bird/day showed inflammation, apoptosis, hemorrhage, necrosis, and leukocytic infiltration tissues of the liver, kidney, and heart of black kites (M. migrans) treated with different concentrations of nimesulide. The treated groups also showed apoptosis of myofibrils and hyperplasia. The hypertrophy, atrophy, fibrosis, necrosis of skeletal muscles and hemorrhage were prominent in the muscles of black kites (M. migrans) intoxicated with nimesulide. All observed histological alterations got worse in a dose-related way. There was no significant difference in AST, ALT, ALP, serum uric acid, but a significant difference was observed in the values of serum urea (p = 0.001) and serum creatinine (p = 0.019).

Keywords:
nimesulide; Milvus migrans ; histological alterations; gout; serum urea; serum creatinine

Parameters	Groups & Dosage (mg/kg body weight of body)	Sampling Days			P Value
Parameters	Groups & Dosage (mg/kg body weight of body)	1^st day	5^th Day	10^th Day	P Value
AST (U/L)	1^st (Control)	407.00±196.00	290.00±12.00	364.50±15.50	0.574
	2^nd (2 mg/kg)	270.00±143.00	466.50±58.50	366.00±145.00
	3^rd (4 mg/kg)	158.50±55.50	395.00±58.00	335.00±104.00
	4^th (6 mg/kg)	288.00±87.00	524.50±46.50	418.50±115.50
ALT(U/L)	1^st (Control)	162.00±5.00	576.50±412.50	114.00±34.00	0.506
	2^nd (2 mg/kg)	60.00±7.00	118.50±3.50	91.00±26.00
	3^rd (4 mg/kg)	183.00±95.00	197.00±75.00	176.50±62.50
	4^th (6 mg/kg)	82.50±24.50	110.00±±33.00	136.50±13.50
ALP (U/L)	1^st (Control)	30.00±1.00	91.50±36.50	63.50±1.50	0.305
	2^nd (2 mg/kg)	64.00±9.00	74.00±34.00	62.00±35.00
	3^rd (4 mg/kg)	43.50±7.50	111.00±11.00	40.00±18.00
	4^th (6 mg/kg)	78.50±19.50	49.00±2.00	47.50±19.50
Serum Urea (mg/dl)	1^st (Control)	5.50±1.50^cd	10.50±0.50^ab	12.50±1.50^a	0.001
	2^nd (2 mg/kg)	10.50±0.50^ab	0.65±0.05^e	3.50±0.50^de
	3^rd (4 mg/kg)	8.50±0.50^bc	5.00±1.00^cd	3.50±1.50^de
	4^th (6 mg/kg)	8.00±1.00^bc	5.25±0.75^cd	5.00±2.00^cd
Serum Uric Acid (mg/dl)	1^st (Control)	22.85±6.45	15.25±0.45	11.10±2.20	0.254
	2^nd (2 mg/kg)	17.55±5.35	17.40±3.80	15.20±0.10
	3^rd (4 mg/kg)	10.10±4.20	16.50±2.50	13.80±0.10
	4^th (6 mg/kg)	10.65±0.95	22.35±7.25	20.10±6.00
Serum Creatinine (mg/dl)	1^st (Control)	0.30±0.10^bcde	0.30±0.00^bcde	0.35±0.05^bcd	0.019
	2^nd (2 mg/kg)	0.50±0.10^ab	0.25±0.05^cde	0.10±0.00^e
	3^rd (4 mg/kg)	0.65±0.05^a	0.15±0.05^de	0.15±0.05^de
	4^th (6 mg/kg)	0.45±0.05^abc	0.15±0.05^de	0.20±0.10^de

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[1] *e-mail: mfarooq@gudgk.edu.pk