Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

doi:10.3748/wjg.v23.i29.5304

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World Journal of Gastroenterology

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1007-9327

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World J Gastroenterol. Aug 7, 2017; 23(29): 5304-5312
Published online Aug 7, 2017. doi: 10.3748/wjg.v23.i29.5304

Table 1 Gastric lesions assessment after celecoxib, BPC 157, L-NAME, L-arginine

Medication (/kg intraperitoneally) immediately after celecoxib 1 g/kg intraperitoneally	Sum of longest lesions diameters (means ± SD, mm) assessed rafter celecoxib and mediation application
	24 h	48 h
Control, saline 5 mL	10 ± 2	17 ± 3.5
BPC 157 10 μg	0 ± 0^a	7.5 ± 2.8^a
BPC 157 10 ng	2 ± 0.8^a	4 ± 1.2^a
BPC 157 1 ng	2.2 ± 0.6^a	4.3 ± 1^a
L-NAME 5 mg	13 ± 2	30 ± 5^a
L-arginine 100 mg	7 ± 1.5	5 ± 1^a
L-NAME 5 mg + L-arginine 100 mg	8 ± 2	10 ± 3^a
L-NAME 5 mg + BPC 157 10 μg	2 ± 1^a	4 ± 2^a
L-NAME 5 mg + BPC 157 10 ng	3.2 ± 0.8^a	5 ± 0.6^a
L-arginine 100 mg + BPC 157 10 μg	1 ± 0.5^a	2.5 ± 0.8^a
L-arginine 100 mg + BPC 157 10 ng	2.3 ± 0.4^a	4.5 ± 0.6^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 μg	1 ± 0.5^a	2.5 ± 0.6^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 ng	2.5 ± 0.4^a	4.7 ± 0.7^a

^aP < 0.05 vs control.

Table 2 Liver lesions assessment after celecoxib, BPC 157, L-NAME, L-arginine

Medication (/kg intraperitoneally) immediately after celecoxib 1 g/kg intraperitoneally	Time after celecoxib	Liver lesions assessment
		Microscopic assessment, Score (0-3), Min/Med/Max			Serum enzymes values (IU/L), means ± SD
		steatosis	congestion	necrosis	ALT	AST
Control, saline 5 mL	24 h	2/2/3	2/2/3	2/2/3	352 ± 12	75 ± 8
Control, saline 5 mL	48 h	2/3/3	2/2/3	2/2/3	356 ± 18	84 ± 9
BPC 157 10 μg	24 h	1/1/1^a	1/1/2^a	1/1/1^a	138 ± 14^a	41 ± 11^a
BPC 157 10 μg	48 h	1/1/1^a	1/1/2^a	1/1/1^a	63 ± 12^a	35 ± 12^a
BPC 157 10 ng	24 h	1/1/1^a	1/1/2^a	1/1/1^a	154 ± 13^a	45 ± 8^a
BPC 157 10 ng	48 h	1/1/2^a	1/1/2^a	1/1/1^a	72 ± 19^a	40 ± 7^a
BPC 157 1 ng	24 h	1/1/1^a	1/1/2^a	1/1/1^a	170 ± 15^a	48 ± 10^a
BPC 157 1 ng	48 h	1/1/2^a	1/1/2^a	1/1/1^a	80 ± 15^a	43 ± 8^a
L-NAME 5 mg	24 h	2/3/3	2/2/3	2/2/3	375 ± 11	86 ± 12
L-NAME 5 mg	48 h	3/3/3	2/3/3	2/2/3	400 ± 12	80 ± 10
L-arginine 100 mg	24 h	1/2/2^a	1/2/2^a	1/2/2^a	315 ± 14^a	68 ± 14^a
L-arginine 100 mg	48 h	1/2/2^a	1/2/2^a	1/2/2^a	300 ± 21^a	65 ± 10^a
L-NAME 5 mg + L-arginine 100 mg	24 h	1/2/2^a	1/2/2^a	1/2/2^a	293 ± 17^a	68 ± 9^a
L-NAME 5 mg + L-arginine 100 mg	48 h	2/2/2	2/2/3	2/2/2	270 ± 15^a	73 ± 11^a
L-NAME 5 mg + BPC 157 10 μg	24 h	1/1/1^a	1/2/2^a	1/1/1^a	170 ± 15^a	69 ± 9^a
L-NAME 5 mg + BPC 157 10 μg	48 h	1/1/2^a	1/2/2^a	1/1/1^a	150 ± 12^a	55 ± 13^a
L-NAME 5 mg + BPC 157 10 ng	24 h	1/1/1^a	1/2/2^a	1/1/1^a	210 ± 16^a	70 ± 7^a
L-NAME 5 mg + BPC 157 10 ng	48 h	1/1/2^a	1/2/2^a	1/1/1^a	182 ± 14^a	60 ± 8^a
L-arginine 100 mg + BPC 157 10 μg	24 h	1/1/1^a	1/1/1^a	1/1/1^a	165 ± 25^a	55 ± 8^a
L-arginine 100 mg + BPC 157 10 μg	48 h	1/1/2^a	1/1/1^a	1/1/1^a	160 ± 18^a	45 ± 8^a
L-arginine 100 mg + BPC 157 10 ng	24 h	1/1/1^a	1/1/2^a	1/1/1^a	190 ± 11^a	63 ± 10^a
L-arginine 100 mg + BPC 157 10 ng	48 h	1/1/2^a	1/1/2^a	1/1/1^a	170 ± 13^a	55 ± 9^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 μg	24 h	1/1/2^a	1/1/2^a	1/1/1^a	167 ± 11^a	57 ± 10^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 μg	48 h	1/1/2^a	1/1/2^a	1/1/1^a	176 ± 14^a	57 ± 8^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 ng	24 h	1/1/2^a	1/1/2^a	1/1/1^a	202 ± 9^a	62 ± 7^a
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 ng	48 h	1/1/2^a	1/1/2^a	1/1/1^a	190 ± 12^a	65 ± 8^a

^aP < 0.05 vs control.

Table 3 Brain lesions assessment after celecoxib, BPC 157, L-NAME, L-arginine

Medication (/kg intraperitoneally) immediately after celecoxib 1 g/kg intraperitoneally	Time after celecoxib	Brain lesions assessment
		Microscopic assessment, Score (0-4),Min/Med/Max		Microscopic assessment, Score (0-3), Min/Med/Max
		Purkinje cells (red neurons)	Cerebral cortex (red neurons)	Edema
Control, saline 5 mL	24 h	2/2/2	2/2/2	0/0/0
Control, saline 5 mL	48 h	2/2/3	2/2/3	0/0/0
BPC 157 10 μg	24 h	0/0/0^a	0/1/1^a	0/0/0
BPC 157 10 μg	48 h	0/1/1^a	0/1/1^a	0/0/0
BPC 157 10 ng	24 h	0/1/1^a	0/1/1^a	0/0/0
BPC 157 10 ng	48 h	0/1/1^a	1/1/1^a	0/0/0
BPC 157 1 ng	24 h	0/1/1^a	0/1/1^a	0/0/0
BPC 157 1 ng	48 h	0/1/1^a	0/1/1^a	0/0/0
L-NAME 5 mg	24 h	2/2/3	2/2/3	0/0/0
L-NAME 5 mg	48 h	2/3/3	2/3/3	0/0/0
L-arginine 100 mg	24 h	1/2/2	1/2/2	0/0/0
L-arginine 100 mg	48 h	1/2/2^a	1/2/2^a	0/0/0
L-NAME 5 mg + L-arginine 100 mg	24 h	2/2/2	2/2/2	0/0/0
L-NAME 5 mg + L-arginine 100 mg	48 h	2/2/2	2/2/2	0/0/0
L-NAME 5 mg + BPC 157 10 μg	24 h	1/1/1^a	1/1/2^a	0/0/0
L-NAME 5 mg + BPC 157 10 μg	48 h	1/1/2^a	1/1/2^a	0/0/0
L-NAME 5 mg + BPC 157 10 ng	24 h	1/1/1^a	1/1/2^a	0/0/0
L-NAME 5 mg + BPC 157 10 ng	48 h	1/1/2^a	1/1/2^a	0/0/0
L-arginine 100 mg+ BPC 157 10 μg	24 h	0/1/1^a	0/1/1^a	0/0/0
L-arginine 100 mg+ BPC 157 10 μg	48 h	1/1/2^a	0/1/1^a	0/0/0
L-arginine 100 mg + BPC 157 10 ng	24 h	0/1/1^a	0/1/1^a	0/0/0
L-arginine 100 mg + BPC 157 10 ng	48 h	1/1/2^a	1/1/1^a	0/0/0
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 μg	24 h	1/1/2^a	1/1/1^a	0/0/0
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 μg	48 h	1/1/2^a	1/1/1^a	0/0/0
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 ng	24 h	1/1/2^a	1/1/1^a	0/0/0
L-NAME 5 mg + L-arginine 100 mg + BPC 157 10 ng	48 h	1/1/2^a	1/2/1^a	0/0/0

^aP < 0.05 vs control.

Citation: Drmic D, Kolenc D, Ilic S, Bauk L, Sever M, Zenko Sever A, Luetic K, Suran J, Seiwerth S, Sikiric P. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME. World J Gastroenterol 2017; 23(29): 5304-5312
URL: https://www.wjgnet.com/1007-9327/full/v23/i29/5304.htm
DOI: https://dx.doi.org/10.3748/wjg.v23.i29.5304