Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

Table 1 Effect of vehicle (saline) and GSE applied ig in graded concentrations ranging from 8 up to 64 mg/kg on the gastric acid secretion and plasma gastrin levels. Results are mean±SE from 6 determinations on 6–8 animals

Type of test	Gastric acid output	Plasma gastrin
	(μmol/30 min)	(pmol/L)
Vehicle	134 ± 11	53 ± 4
GSE (mg/kg ig)
8	131 ± 9	56 ± 6
16	118 ± 9a	69 ± 8a
32	89 ±7a	75 ± 9a
64	64 ± 5a	82 ± 10a

^aP<  0.05 vs vehicle.

Table 2 Effect of vehicle (saline) and GSE applied i.g. in graded concentrations ranging from 8 mg/kg up to 64 mg/kg on the MDA concentration and SOD activity in the gastric mucosa in rats exposed to 100% ethanol or those subjected to 3.5 h of WRS. Results are mean±SE from 6 determinations on 6–8 animals

Type of test	MDA concentration	SOD activity
	(nmol/g)	(unit/g)
Intact	0.5 ± 0.02	733 ± 43
Vehicle+ethanol	14.8  ± 2.3a	425 ± 32a
Vehicle+WRS	16.8 ± 2.3a	425 ± 32a
GSE (mg/kg i.g.)+ethanol
8	13.7 ± 2.3	438 ± 37
16	10.4 ± 2.8c	549 ± 38c
32	8.3 ± 0.9c	675 ± 40c
64	6.6 ± 0.7c	695 ± 43c
GSE (mg/kg i.g.)+WRS
8	15.7 ± 2.6c	438 ± 37c
16	13.4 ± 2.3c	549 ± 38c
32	10.3 ± 1.9c	675 ± 40c
64	8.6 ± 0.8c	695 ± 43c

^aP < 0.05 vs intact,

^cP < 0.05 vs vehicle+ethanol or vehicle+WRS.

Table 3 Effect of GSE with or without pretreatment with NG-nitro-L-arginine (L-NNA 20 mg/kg ip) applied with or without the combination with L-arginine (L-Arg, 200 mg/kg ig) or D-arginine (D-Arg, 200 mg/kg ig) on the area of ethanol-induced gastric lesions and accompanying changes in the GBF. Results are mean±SE of 6–8 rats

Type of test	Mean lesion area (mm2)	GBF (% control)
Without L-NNA
Vehicle	82 ± 5	63 ± 3
GSE (32 mg/kg i.g.)	8 ± 1.5a	81 ± 4a
With L-NNA
Vehicle	88 ± 4	58 ± 3
GSE (32 mg/kg i.g.)	76±3c	66 ± 5c
L-Arg (200 mg/kg i.g.)
+GSE (32 mg/kg i.g.)	12 ± 2c	79 ± 3c
D-Arg (200 mg/kg i.g.)
+GSE (32 mg/kg i.g.)	72 ± 4	69 ± 3

^aP < 0.05 vs vehicle,

^cP < 0.05 vs values in respective group without L-NNA, ^eP < 0.05 vs values in respective group with L-NNA but without L-Arg administration.

Table 4 The number of WRS-induced gastric lesions and accompanying changes in the GBF in rats treated with vehicle and GSE (32 mg/kg i.g.) without or with capsaicin denervation. Means±SE of 6–8 rats

Type of test	Mean lesion number	GBF (% control)
Without capsaicin denervation
Vehicle	18 ± 3	67 ± 4
GSE (32 mg/kg ig)	8 ± 1.5a	78 ± 3a
With capsaicin denervation
Vehicle	28 ± 4b	54 ± 3b
GSE (32 mg/kg ig)	16 ± 3b	64 ± 4b
CGRP (10 μg/kg sc)
+GSE (32 mg/kg ig)	9 ± 1.3c	74 ± 3c

^aP < 0.05 vs vehicle,

^cP < 0.05 vs corresponding values obtained in animals without capsaicin denervation, ^eP < 0.05 vs corresponding values obtained in animals with capsaicin denervation without CGRP treatment.