Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect

doi:10.3748/wjg.v29.i27.4289

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World Journal of Gastroenterology

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World J Gastroenterol. Jul 21, 2023; 29(27): 4289-4316
Published online Jul 21, 2023. doi: 10.3748/wjg.v29.i27.4289

Table 1 Blood pressures and thrombosis in rats at 15 min and 60 min following stomach perforation

Application of the 1 mL/rat through the perforated defect in the injured stomach at 5 min following perforation	Blood pressures and thrombosis in rats at 15 min and 60 min following stomach perforation
	15 min	60 min
Superior sagittal sinus pressure, mmHg, mean ± SD
Control	9 ± 1	8 ± 1
BPC 157 10 μg/kg	-3 ± 1^a	-1 ± 1^a
BPC 157 10 ng/kg	-1 ± 1^a	-2 ± 1^a
Portal pressure, mmHg, mean ± SD
Control	16 ± 2	17 ± 1
BPC 157 10 μg/kg	9 ± 1^a	9 ± 1^a
BPC 157 10 ng/kg	9 ± 1^a	8 ± 1^a
Caval pressure, mmHg, mean ± SD
Control	15 ± 1	15 ± 1
BPC 157 10 μg/kg	8 ± 1	9 ± 1^a
BPC 157 10 ng/kg	7 ± 1	9 ± 1^a
Aortal pressure, mmHg, mean ± SD
Control	42 ± 5	45 ± 7
BPC 157 10 μg/kg	75 ± 4^a	72 ± 5^a
BPC 157 10 ng/kg	80 ± 5^a	78 ± 7^a
Superior sagittal sinus, thrombus mass, g, mean ± SD
Control	0.0012 ± 0.0005	0.0022 ± 0.0009
BPC 157 10 μg/kg	0 ± 0^a	0 ± 0^a
BPC 157 10 ng/kg	0 ± 0^a	0 ± 0^a
Portal vein, thrombus mass, g, mean ± SD
Control	0.0034 ± 0.0006	0.0056 ± 0.0008
BPC 157 10 μg/kg	0.0010 ± 0.0005^a	0.0020 ± 0.0005^a
BPC 157 10 ng/kg	0.0010 ± 0.0007^a	0.0018 ± 0.0006^a
Inferior caval vein, thrombus mass, g, mean ± SD
Control	0.0039 ± 0.0007	0.0061 ± 0.0008
BPC 157 10 μg/kg	0.0002 ± 0.0001^a	0.0003 ± 0.0001^a
BPC 157 10 ng/kg	0.0008 ± 0.0001^a	0.0005 ± 0.0002^a
Abdominal aorta, thrombus mass, g, mean ± SD
Control	0.0044 ± 0.0007	0.0063 ± 0.0009
BPC 157 10 μg/kg	0 ± 0^a	0 ± 0^a
BPC 157 10 ng/kg	0 ± 0^a	0 ± 0^a

^aP < 0.05, at least vs control.

Blood pressures (intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, mmHg), and thrombosis (thrombus mass, g) in rats at 15 min and 60 min following perforation of the stomach. Saline (5 mL/kg) (control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min thereafter.

Table 2 Relative volume of the stomach of the heart, azygos vein, in rats at 5 min and 15 min following stomach perforation

0 min	5 min	5 min	15 min
Relative volume (healthy/perforation, %) of the stomach in rats immediately after perforation	Application of the 1 mL/rat through the perforated defect in the injured stomach at 5 min following perforation	Relative volume (healthy/perforation, healthy/perforation + therapy, %) of the stomach, in rats at 5 min and 15 min following stomach perforation
Relative volume (healthy/perforation, %) of the stomach, mean ± SD	Medication	Relative volume (healthy/perforation + therapy, %) of the stomach, mean ± SD
100 ± 3	Saline 5 mL/kg (control)	114 ± 2^a^,^b	118 ± 2^a^,^b
100 ± 2	BPC 157 10 μg/kg	87 ± 5^a^,^b^,^c	76 ± 8^a^,^b^,^c
101 ± 2	BPC 157 10 ng/kg	81 ± 7^a^,^b^,^c	79 ± 9^a^,^b^,^c

^aP < 0.05, at least vs healthy.

^bP < 0.05, at least vs immediately after perforation.

^cP < 0.05, at least vs corresponding control at the time of the assessment.

Relative volume (healthy/perforation, healthy/perforation + therapy, %) of the stomach of the heart, azygos vein, in rats at 5 min and 15 min following stomach perforation. Saline (5 mL/kg, control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min after perforation.

Table 3 Relative volume of the brain, inferior caval vein, and superior mesenteric vein, and relative volume of the heart, azygos vein, in rats at 15 min and 60 min following stomach perforation

0 min	5 min	15 min	60 min
Relative volume (healthy/perforation, %) of the brain, heart, azygos vein, inferior caval vein, superior mesenteric vein, and abdominal aorta in rats immediately after perforation	Application of the 1 mL/rat through the perforated defect in the injured stomach at 5 min following perforation	Relative volume (healthy/perforation, healthy/perforation + therapy, %) of the brain, inferior caval vein, and superior mesenteric vein, and relative volume (control/treated, %) of the heart, azygos vein, in rats at 15 min and 60 min following stomach perforation
Relative volume (healthy/perforation) (%) of the brain, mean ± SD	Medication	Relative volume (healthy/perforation + therapy, %) of the brain, mean ± SD
116 ± 3^a	Saline 5 mL/kg (control)	124 ± 2^a^,^b	124 ± 2^a^,^b
120 ± 2^a	BPC 157 10 μg/kg	100 ± 1^b^,^c	99 ± 2^b^,^c
121 ± 2^a	BPC 157 10 ng/kg	101 ± 3^b^,^c	100 ± 1^b^,^c
-	Relative volume (control/treated, %) of the heart, mean ± SD
	BPC 157 10 μg/kg	137 ± 4^c	141 ± 5^c
	BPC 157 10 ng/kg	136 ± 3^c	138 ± 4^c
	Relative volume (control/treated, %) of the azygos vein, mean ± SD
	BPC 157 10 μg/kg	66 ± 6^c	58 ± 7^c
	BPC 157 10 ng/kg	64 ± 4^c	54 ± 8^c
	Relative volume (healthy/perforation + therapy, %) of the inferior caval vein, mean ± SD
130 ± 3^a	Saline 5 mL/kg (control)	164 ± 8^a^,^b	174 ± 9^a^,^b
128 ± 4^a	BPC 157 10 μg/kg	98 ± 2^b^,^c	100 ± 2^b^,^c
126 ± 4^a	BPC 157 10 ng/kg	100 ± 3^b^,^c	99 ± 1^b^,^c
	Relative volume (healthy/perforation + therapy, %) of the superior mesenteric vein, mean ± SD
180 ± 5^a	Saline 5 mL/kg (control)	204 ± 8^a^,^b	212 ± 9^a^,^b
188 ± 9^a	BPC 157 10 μg/kg	96 ± 6^b^,^c	99 ± 7^b^,^c
186 ± 8^a	BPC 157 10 ng/kg	98 ± 6^b^,^c	101 ± 1^b^,^c

^aP < 0.05, at least vs healthy.

^bP < 0.05, at least vs immediately after perforation.

^cP < 0.05, at least vs corresponding control at the time of the assessment.

Relative volume (healthy/perforation, healthy/perforation + therapy, %) of the brain, inferior caval vein, and superior mesenteric vein, and relative volume (control/treated, %) of the heart, azygos vein, in rats at 15 min and 60 min following stomach perforation. Saline (5 mL/kg) (control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min after perforation.

Table 4 ECG changes, PQ interval, QTc interval, msec, heart frequency, beats/min, in rats at 15 min and 60 min following stomach perforation

Application of the 1 mL/rat through the perforated defect in the injured stomach at 5 min following perforation	ECG changes in rats at 15 min and 60 min following stomach perforation
	15 min	60 min
	PQ interval, msec mean ± SD
Control	64 ± 5	67 ± 6
BPC 157 10 μg/kg	50 ± 5^a	50 ± 5^a
BPC 157 10 ng/kg	50 ± 5^a	50 ± 5^a
	QTc interval, msec, mean ± SD
Control	312 ± 10	347 ± 10
BPC 157 10 μg/kg	180 ± 10^a	188 ± 10^a
BPC 157 10 ng/kg	185 ± 10^a	183 ± 10^a
	Heart frequency, beats/min, mean ± SD
Control	530 ± 30	550 ± 30
BPC 157 10 μg/kg	375 ± 10 ^a	360 ± 10^a
BPC 157 10 ng/kg	385 ± 10 ^a	365 ± 10^a

^aP < 0.05, at least vs control.

ECG changes, PQ interval, QTc interval, msec, heart frequency, beats/min, in rats at 15 min and 60 min following stomach perforation. Saline (5 mL/kg, control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min thereafter.

Table 5 Lesions scored microscopically (heart, lung, liver, kidney, stomach), or macroscopically (stomach, in rats at 15 min and 60 min following stomach perforation

Application of the 1 mL/rat through the perforated defect in the injured stomach at 5 min following perforation	Lesions scored microscopically (heart, lung, liver, kidney, stomach, small and large intestine), or macroscopically (stomach), in rats at 15 min and 60 min following stomach perforation
	15 min	60 min
	Heart (scored 0-3, min/med/max)
Control	3/3/3	3/3/3
BPC 157 10 μg/kg	0/0/0^a	0/0/0^a
BPC 157 10 ng/kg	0/0/0^a	0/0/0^a
	Lung (scored 0-3, min/med/max)
Control	3/3/3	3/3/3
BPC 157 10 μg/kg	1/1/1^a	1/1/1^a
BPC 157 10 ng/kg	1/1/1^a	1/1/1^a
	Liver (scored 0-3, min/med/max)
Control	3/3/3	3/3/3
BPC 157 10 μg/kg	0/0/0^a	0/0/0^a
BPC 157 10 ng/kg	0/0/0^a	0/0/0^a
	Kidney (scored 0-3, min/med/max)
Control	3/3/3	3/3/3
BPC 157 10 μg/kg	0/0/0^a	0/0/0^a
BPC 157 10 ng/kg	0/0/0^a	0/0/0^a
	Stomach (scored 0-15, min/med/max)
Control	5/5/5	4/5/5
BPC 157 10 μg/kg	1/1/1^a	1/1/1^a
BPC 157 10 ng/kg	1/1/1^a	1/1/1^a

^aP < 0.05, at least vs control.

Lesions scored microscopically (heart, lung, liver, kidney, and stomach), or macroscopically (stomach, in rats at 15 min and 60 min following stomach perforation. Saline (5 mL/kg, control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min thereafter.

Table 6 Lesions were assessed microscopically (cerebrum, cerebellum, hypothalamus, hippocampus), in rats at 15 min and 60 min following stomach perforation

Application of the 1 ml/rat through the perforated defect in the injured stomach at 5 min following perforation	Lesions scored microscopically cerebrum, cerebellum, hypothalamus, and hippocampus in rats at 15 min and 60 min following stomach perforation
	15 min	60 min
	Cerebrum (scored 0-8, min/med/max); percentage of karyopycnotic cells (%), mean ± SD
Control	2/2/2; 30 ± 5	2/2/2, 35 ± 5
BPC 157 10 μg/kg	0/1/1^a, 5 ± 5^a	0/1/1^a, 5 ± 5^a
BPC 157 10 ng/kg	0/1/1^a, 5 ± 5^a	0/1/1^a, 5 ± 5^a
	Neuronal damage in the karyopyknotic areas, %, mean ± SD (10 HPF, 400 ×)
Control	39 ± 5	42 ± 4
BPC 157 10 μg/kg	2 ± 2^a	3 ± 2^a
BPC 157 10 ng/kg	2 ± 2^a	2 ± 2^a
	Hemorrhage (% of total area), mean ± SD
Control	30 ± 2	25 ± 2
BPC 157 10 μg/kg	5 ± 2^a	5 ± 2^a
BPC 157 10 ng/kg
	Edema (scored 0-3, min/med/max)
Control	37683	37683
BPC 157 10 μg/kg	1/1/1^a	1/1/1^a
BPC 157 10 ng/kg	1/1/1^a	1/1/1^a
	Cerebellum (scored 0-8, min/med/max); percentage of karyopycnotic cells (%), mean ± SD
Control	1/2/2, 13 ± 5	1/1/1, 15 ± 5
BPC 157 10 μg/kg	0/0/1^a, 5 ± 5^a	0/0/1^a, 5 ± 5^a
BPC 157 10 ng/kg	0/0/1^a, 5 ± 5^a	0/0/1^a, 5 ± 5^a
	Neuronal damage in the karyopyknotic areas (%), mean ± SD (10 HPF, 400 ×)
Control	27 ± 4	23 ± 5
BPC 157 10 μg/kg	0 ± 0^a	0 ± 0^a
BPC 157 10 ng/kg	0 ± 0^a	0 ± 0^a
	Hemorrhage (% of total area), mean ± SD
Control	0 ± 0	0 ± 0
BPC 157 10 μg/kg	0 ± 0	0 ± 0
BPC 157 10 ng/kg	0 ± 0	0 ± 0
	Edema (scored 0-3, min/med/max)
Control	37683	37318
BPC 157 10 μg/kg	0/0/1^a	0/0/1^a
BPC 157 10 ng/kg	0/0/1^a	0/0/1^a
	Hippocampus (scored 0-8, min/med/max); percentage of karyopycnotic cells (%), mean ± SD
Control	37289	36924
Control	25 ± 3	28 ± 2
BPC 157 10 μg/kg	0/0/0^a, 0 ± 0^a	0/0/0^a, 0 ± 0^a
BPC 157 10 ng/kg	0/0/0^a, 0 ± 0^a	0/0/0^a, 0 ± 0^a
	Neuronal damage in the karyopyknotic areas (%), mean ± SD (10 HPF, 400 ×)
Control	23 ± 2	24 ± 3
BPC 157 10 μg/kg	0 ± 0^a	0 ± 0^a
BPC 157 10 ng/kg	0 ± 0^a	0 ± 0^a
	Hemorrhage (% of total area), mean ± SD
Control	0 ± 0	0 ± 0
BPC 157 10 μg/kg	0 ± 0	0 ± 0
BPC 157 10 ng/kg	0 ± 0	0 ± 0
	Edema (scored 0-3, min/med/max)
Control	37683	37318
BPC 157 10 μg/kg	0/0/0^a	0/0/0^a
BPC 157 10 ng/kg	0/0/0^a	0/0/0^a
	Hypothalamus (scored 0-8, min/med/max); percentage of karyopycnotic cells (%), mean ± SD
Control	2/2/2, 31 ± 3	1/1/1, 29 ± 4
BPC 157 10 μg/kg	0/0/1^a, 5 ± 5^a	0/0/1^a, 5 ± 5^a
BPC 157 10 ng/kg	0/0/1^a, 5 ± 5^a	0/0/1^a, 5 ± 5^a
	Neuronal damage in the karyopyknotic areas (%), mean ± SD (10 HPF, 400 ×)
Control	24 ± 3	28 ± 5
BPC 157 10 μg/kg	5 ± 2^a	6 ± 3^a
BPC 157 10 ng/kg	5 ± 2^a	6 ± 3^a
	Hemorrhage (% of total area), mean ± SD
Control	0 ± 0	0 ± 0
BPC 157 10 μg/kg	0 ± 0	0 ± 0
BPC 157 10 ng/kg	0 ± 0	0 ± 0
	Edema (scored 0-3, min/med/max)
Control	37683	37318
BPC 157 10 μg/kg	0/1/1^a	0/1/1^a
BPC 157 10 ng/kg	0/1/1^a	0/1/1^a

^aP < 0.05, at least vs control.

Lesions were assessed microscopically (cerebrum, cerebellum, hypothalamus, and hippocampus), in rats at 15 min and 60 min following stomach perforation. Saline (5 mL/kg, control) or BPC 157 (10 μg/kg and 10 ng/kg) were given at 5 min thereafter.

Citation: Kalogjera L, Krezic I, Smoday IM, Vranes H, Zizek H, Yago H, Oroz K, Vukovic V, Kavelj I, Novosel L, Zubcic S, Barisic I, Beketic Oreskovic L, Strbe S, Sever M, Sjekavica I, Skrtic A, Boban Blagaic A, Seiwerth S, Sikiric P. Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect. World J Gastroenterol 2023; 29(27): 4289-4316
URL: https://www.wjgnet.com/1007-9327/full/v29/i27/4289.htm
DOI: https://dx.doi.org/10.3748/wjg.v29.i27.4289