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

Figure 1 Effect of intragastric (ig) pretreatment with GSE applied in graded doses ranging from 8 mg/kg up to 64 mg/kg or 16,16 dimethyl PGE₂ (5 μg/kg ig) on the mean area of gastric lesions induced by ethanol and accompanying changes in the GBF. Results are mean±SE from 6 to 8 animals per group. ^aP<0.05 vs vehicle (Veh).

Figure 2 Effect of intragastric (ig) pretreatment with GSE applied in graded doses ranging from 8 mg/kg up to 64 mg/kg or 16,16 dimethyl PGE₂ (5 μg/kg ig) on the mean number of gastric lesions induced by 3. 5 h of WRS and accompanying changes in the GBF. Results are mean ± SE from 6 to 8 animals per group. ^aP < 0.05 vs vehicle (Veh).

Figure 3 Effect of GSE (32 mg/kg ig) on the mean number of WRS-induced gastric lesions and accompanying alterations in the gastric mucosal PGE2 generation and GBF in rats with or without the pretreatment with indomethacin (5mg/kg ip) or rofecoxib (10 mg/kg ig). Results are mean±SE from 6 to 8 animals per group. ^aP<0.05 vs vehicle (Veh), ^cP<0.05 vs respective values in animals without indomethacin or rofecoxib pretreatment.

Figure 4 Effect of GSE (32 mg/kg i. g.) on the mean number of WRS-induced gastric lesions and accompanying alterations in the GBF in rats with or without the pretreatment with L-NNA (20 mg/kg i.p.). Results are mean ±SE from 6-8 animals per group. ^aP < 0.05 vs vehicle (Veh), ^bP < 0.01 vs respective values in animals without L-NNA administration, ^cP < 0.05 vs respective values in animals treated with L-NNA. vs vehicle (Veh), ^bP < 0.01 vs respective values in animals without indomethacin or rofecoxib pretreatment.

Figure 5 Effect of GSE (32 mg/kg ig) on the mean area of ethanol-induced gastric lesions and accompanying alterations in the GBF in rats with or without capsaicin inactivation of sensory nerves. Results are mean±SE from 6–8 animals per group. ^aP < 0.05 vs vehicle (Veh), ^bP < 0.01 vs respective values in animals without capsaicin denervation, ^cP < 0.05 vs respective values in animals with capsaicin denervation. administration, ^cP < 0.05 vs respective values in animals treated with L-NNA. vs vehicle (Veh), ^bP < 0.01 vs respective values in animals without indomethacin or rofecoxib pretreatment.

Figure 6 Determination of SOD mRNA (left panel) by RT-PCR and by ratio of SOD mRNA over β-actin (right panel) in the vehicle-control intact gastric mucosa (lane 1) and in those treated with GSE given i. g. in graded doses of 16 mg/kg (lane 2), 32 mg/kg (lane 3) and 64 mg/kg (lane 4) prior to the exposure to ethanol, M-DNA size marker, NC-negative control. Mean±SE of 4–6 rats. ^aP < 0.05 vs vehicle (Veh), ^bP < 0.01 vs ethanol alone group. ^cP < 0.05 vs respective values in animals with capsaicin denervation. administration, ^cP < 0.05 vs respective values in animals treated with L-NNA. vs vehicle (Veh), ^bP < 0.01 vs respective values in animals without indomethacin or rofecoxib pretreatment.