Serotonin and histamine mediate gastroprotective effect of fluoxetine against experimentally-induced ulcers in rats

Figures & data

Table 1. Animal body weights at Days 1, 7 and 14 of experiment.

	Day 1	Day 7	Day 14
Control (1)	189.4 ± 3.6	196.4 ± 4.8^a	205.0 ± 4.8^a^b
Indomethacine (INDO)	189.0 ± 5.8	198.2 ± 5.0^a	208.4 ± 6.4^a^b
Ranitidine + INDO	188.6 ± 4.9	191.0 ± 4.3	189.8 ± 4.7
Fluoxetine + INDO	191.4 ± 8.0	168.8 ± 9.3^a	153.6 ± 5.0^a^b
Control (2)	192.0 ± 2.3	200.0 ± 4.3^a	209.8 ± 5.9^a^b
Alcohol	191.8 ± 6.7	200.2 ± 6.4^a	209.2 ± 6.7^a^b
Ranitidine + alcohol	186.6 ± 3.6	188.4 ± 4.4	190.4 ± 4.4
Fluoxetine + alcohol	191.8 ± 7.2	170.4 ± 8.1^a	152.0 ± 5.1^a^b

a p < 0.05 statistically significance as compared to weight of rats on Day 1.

b p < 0.05 statistically significance as compared to weight of rats on Day 7.

Data are presented as mean (± SD) (n = 7/group); all values in terms of grams.

Table 2. Effects on gastric ulcer score, pH, NO and serotonin contents.

	Ulcer score (mm^2)	Gastric pH	NO (μM/g tissue)	Serotonin (nmole/g tissue)
Control (1)	0	2.77 ± 0.12	25.80 ± 1.11	188.40 ± 11.30
Indomethacin (INDO)	12.4 ± 1.81	1.96 ± 0.12^a	12.10 ± 1.12^a	87.34 ± 9.81^a
Ranitidine + INDO	1.20 ± 0.74^b	2.93 ± 0.13^b	21.09 ± 1.78^b	171.42 ± 11.71^b
Fluoxetine + INDO	1.10 ± 0.22^b	2.97 ± 0.08^b	27.52 ± 1.56^b^c	193.48 ± 9.83^b^c
Control (2)	0	3.11 ± 0.14	25.54 ± 1.69	182.18 ± 5.25
Alcohol	134.80 ± 12.77	2.10 ± 0.08^d	5.84 ± 1.12^d	52.84 ± 4.52^d
Ranitidine + Alcohol	64.47 ± 4.47^e	2.62 ± 0.17^e	12.92 ± 0.87^e	114.66 ± 10.49^e
Fluoxetine + Alcohol	1.50 ± 0.51^e^f	3.01 ± 0.09^e^f	23.40 ± 1.68^e^f	190.82 ± 12.70^e^f

Data are presented as mean (± SD) (n = 7/group).

a p < 0.05, statistically significance as compared to control (1) group.

b p < 0.05, statistically significance as compared to indomethacin induced ulcer group.

c p < 0.05, statistically significance as compared to (ranitidine + indomethacin) group.

d p < 0.05, statistically significance as compared to control (2) group .

e p < 0.05, statistically significance as compared to alcohol induced ulcer group.

f p < 0.05, statistically significance as compared to (ranitidine + alcohol) group.

Table 3. Effects on gastric histamine, TNFα, MPO and GSH content.

	Histamine (ng/g tissue)	TNFα (pg/g tissue)	MPO (U/mg protein)	GSH (μM/g tissue)
Control (1)	14.76 ± 0.77	146.6 ± 10.2	0.35 ± 0.05	199.40 ± 6.66
Indomethacin (INDO)	7.15 ± 0.76^a	532.2 ± 52.6^a	0.74 ± 0.09^a	43.62 ± 7.92^a
Ranitidine + INDO	11.22 ± 0.60^b	123.2 ± 23.9^b	0.426 ± 0.06^b	156.27 ± 12.19^b
Fluoxetine + INDO	12.90 ± 1.12^b^c	178.2 ± 30.1^b^c	0.31 ± 0.05^b^c	166.08 ± 8.00^b
Control (2)	14.50 ± 1.07	145.0 ± 11.0	0.33 ± 0.04	206.40 ± 9.32
Alcohol	6.46 ± 0.86^d	613.0 ± 77.0^d	0.87 ± 0.11^d	30.03 ± 4.12^d
Ranitidine + Alcohol	9.62 ± 0.86^e	284.0 ± 80.0^e	0.51 ± 0.03^e	95.40 ± 16.95^e
Fluoxetine + Alcohol	13.52 ± 1.30^e^f	114.8 ± 37.0^e^f	0.25 ± 0.01^e^f	187.55 ± 9.09^e^f

Data are presented as mean (± SD) (n = 7/group).

a p < 0.05, statistically significant vs control (1) group.

b p < 0.05, statistically significant vs INDO-induced ulcer group.

c p < 0.05, statistically significant vs (ranitidine + indomethacin) group.

d p < 0.05, statistically significant vs control (2) group.

e p < 0.05, statistically significant vs alcohol induced ulcer group.

f p < 0.05, statistically significant vs.(ranitidine + alcohol) group.

Figure 1. Rat gastric mucosa. (A, E) Normal gastric mucosa in Control group 1 and 2 rats, respectively. (B) Deep ulceration with sloughing of tissue till the basal gland in INDO rat. (C) Healing of mucosa starting from the basal area of ulcer in ranitidine + INDO rat. (D) Healing of mucosa starting from the basal area of the ulcer in fluoxetine + INDO rat. (F) Superficial ulceration that does not involve whole thickness of mucosa, with mononuclear cell infiltration in alcohol-only rat. (G) Mild superficial ulceration with mononuclear cells infiltration in ranitidine + alcohol rat. (H) Healing from basal ulcer in fluoxetine + alcohol rat. Representative photo-micrographs from each group are shown. (H&E; magnification = 40×).

Figure 2. COX-1 expression in rat gastric mucosa. (A, E) Highly positive (+++) constitutive expression of COX-1 in gastric mucosa of Control groups 1 and 2 rats, respectively. (B) Negative (±) expression in INDO rat. (C): negative (±) expression in ranitidine + INDO rat. (D) Moderate (++) expression in fluoxetine + INDO rat. (F) Weak positive (+) expression in alcohol-only rat. (G) Negative expression (±) in ranitidine + alcohol rat. (H) Moderate (++) expression in fluoxetine + alcohol rat. Representative photomicrographs from each group are shown. (PAP; magnification = 40×).

Figure 3. COX-2 expression in rat gastric mucosa. (A, E) Highly positive (+++) expression of COX-2 in gastric mucosa of Control groups 1 and 2 rats, respectively. (B) Negative (±) expression in INDO rat. (C) Moderate positive (++) expression in ranitidine + INDO rat. (D) Highly positive (+++) expression in fluoxetine + INDO rat. (F) Highly positive (+++) expression around the rim of the ulcer in alcohol-only rat. (G) Highly positive (+++) expression around remaining ulceration in ranitidine + alcohol rat. (H) Highly positive (+++) expression in fluoxetine + alcohol rat. Representative photomicrographs from each group are shown (PAP; magnification = 40×).