Potassium bromate cytotoxicity in the Wister rat model of chronic gastric ulcers: Possible reversal by protocatechuic acid.

The interaction between ingested xenobiotics and the gastrointestinal epithelium influences the possibility of gut epithelial cytotoxicity and systemic toxicity. Potassium bromate (KBrO3 ) has been shown to perturb the central nervous system and it may be carcinogenic, albeit it is used as a food additive. This highlights the need to understand KBrO3 's effect on the stomach epithelium. Here, we report the cytotoxic potential of KBrO3 in an ulcerated stomach, as well as possible cytoprotection by the polyphenol - protocatechuic acid. Potassium bromate (12.5 mg/kg) and protocatechuic acid (120 mg/kg) were administered orally while omeprazole (20 mg/kg) was used as standard. Potassium bromate exacerbated gastric ulcers, increased malonaldehyde levels, catalase, and sodium pump activities, but reduced nitric oxide levels. Potassium bromate further increased mast cell count in the muscularis mucosa, while inducing chronic inflammation and moderate angiogenesis in the gastric mucosa. Our results delineate KBrO3 -induced gastric epithelial cytotoxicity that is ameliorated by protocatechuic acid. PRACTICAL APPLICATIONS: Potassium bromate is a known food additive in the baking, brewing, and cheese-making process. Conversely, protocatechuic acid (3,4-dihydroxybenzoic acid) is the polyphenolic content of plants like Hibiscus sabdariffa L that are commonly consumed as herbal drink, food, spices, and used in folk medicine. This study reports the cytoprotective effect of protocatechuic acid against gastric mucosa ulceration that has been aggravated by potassium bromate.

An Editor bows out - Tribute to former Editor, Prof. Anthony Ebeigbe as he retires.

This tribute was written to appreciate the longest-serving Editor-in-Chief in the history of this journal as he retires from active teaching and research. His contributions to the Physiological Society of Nigeria is outstanding and his relationship with colleagues highly commendable.

Exposure to Mosquito Coil Smoke Delays Healing of Acetic Acid Induced Gastric Ulcer in Male Wistar Rats.

Mosquito coil fumes (MCF) is used in several Nigerian homes and some part of the world with reported grave consequences to the respiratory tract majorly. There is paucity of information on its outcome on the gastrointestinal tract being a related organ to the respiratory tract. Forty five male Wistar rats (123.1 ± 7.3g) were used in this study, they were grouped into 3 (n=15/group; 5 each day of experiment). Rats in group 1 served as control (no MCF). Groups 2 and 3 were exposed to MCF for 8-10 h daily for 2 (2p) and 6 (6p) weeks respectively, in a well-ventilated room of 38.3m3 in size each day. After the period of exposure, chronic gastric ulcer were induced by intraluminal application of 50% acetic acid. The animals were sacrificed on days 0 (no ulcer induction), 3 and 10 post ulceration for complete blood count and ulcer scores. Stomach was excised for histology and biochemical assays, homogenized gastric tissues were analyzed by spectrophotometry for malondialdehyde (MDA), catalase and nitric oxide (NO) estimations. Data were expressed as mean ± SEM. Gross ulcer area (mm3) increased significantly on days 3 and 10 in 6p (167.3±16.03; 65.20±3.93) and 2p (152.7±6.20; 68.70±3.45) compared to control (93.26±2.80; 34.82 ±1.84) respectively. Lymphocytes count (%) decreased significantly on day 3 in 2p (60.60 ±1.97) compared to control (70.60 ± 0.87), Neutrophil count (%) in 6p (36.40 ±1.08: 30.20 ±1.46) increased significantly compared with control (25.60±0.80; 26.00 ±1.58) on day 3 and 10 respectively. MDA concentration in 6p and 2p increased significantly compared to control on day 3. Nitric oxide decreased significantly in 6p and 2p on day 3and 10 compared to control. Mosquito coil fumes proofs toxic to the stomach especially to inflamed rats stomach by delaying healing of gastric ulcer through reduction in NO and raised oxidative stress markers.

Anti-ulcerogenic effect of the methanol extract of Chasmanthera dependens (Hochst) stem on male Wistar rats.

Background Oxidative stress and free radical-mediated processes have been implicated in the pathogenesis of indomethacin-induced gastric ulcer. This study investigated the ability of the methanol extract of Chasmanthera dependens to protect the gastric mucosal from oxidative damage induced by oral administration of indomethacin in rats. Methods The C. dependens stems were chopped into pieces, air-dried, and pulverized into powder. One kilogram of the powder was macerated in 1 L of methanol for 72 h. The mixture was filtered and evaporated using rotatory evaporator to obtain the extract of C. dependens. Adult male rats were divided into eight groups of six animals per group and were pretreated orally with the methanol extract of C. dependens (200, 400, and 800 mg/kg) or cimetidine (CIM), a standard drug (50 mg/kg), for 7 days. Gastric ulcer was induced orally with indomethacin. Ulcerogenic parameters, oxidative stress indices, and histopathological examination of the stomach were assessed to monitor the gastroprotective potential of C. dependens stem. Results Indomethacin caused severe gastric mucosa damage and significant reduction in the gastric mucosa antioxidant system with concomitant increase in the level of lipid peroxidation. Pretreatment with the methanol extract of C. dependens or CIM significantly reduced the formation of ulcer at the different doses administered. Similarly, pretreatments with the extract or CIM improved the antioxidant system, decreased acid output, lipid peroxidation, and improved the architecture of the gastric mucosa in ulcerated rats. Conclusions The results show the gastroprotective effect of the methanolic extract of C. dependens, which may be attributed to its antioxidant properties.

Accelerated gastric ulcer healing in thyroxine-treated rats: roles of gastric acid, mucus, and inflammatory response.

The roles of gastric acid, mucus, and inflammation on the pro-ulcer-healing effect of thyroid hormone were investigated. Male Wistar rats were randomly divided into four groups: control, thyroidectomised, thyroidectomised with thyroxine treatment (100 µg·kg-1·day-1), and sham-operated animals treated with thyroxine. Thirty-five days after thyroidectomy, sham surgery, or thyroxine treatment, an ulcer was experimentally induced. Healing was assessed 3, 7, and 10 days post-ulceration by measurement of the ulcer area, gastric mucus and acid secretion, and neutrophil lymphocyte ratio (NLR) as an index of inflammation. By day 10, the ulcer area had decreased in all groups. Recovery was significantly greater (P < 0.05) in thyroxine-treated rats (78.5% ± 1.6% reduction in ulcer area) than in controls (72.3% ± 1.2% reduction) or thyroidectomised rats (63.3% ± 1.9% reduction). Thyroxine-treated animals also had the highest reduction in NLR (65.0% ± 2.5%). Mucus secretion was significantly lower (P < 0.05) in thyroidectomised rats by days 3 and 7. Furthermore, by day 10, the concentration of basal acid decreased by 77.4% ± 2.6% in thyroxine-treated, 65.0% ± 0.0% in control, and 51.5% ± 3.3% in thyroidectomised rats. We conclude that thyroxine accelerates gastric ulcer healing by altering mucus and acid secretion and reducing NLR.

Testicular toxicity and sperm quality following cadmium exposure in rats: Ameliorative potentials of Allium cepa.

AIMS: This study was carried out to investigate the effect of Allium cepa crude extract on cadmium-induced testicular toxicity in rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were randomized into 4 groups (n = 6). Group 1 was used as control, group 2 was administered 0.3 mg/kgBW of cadmium sulfate (CdSO(4)) intraperitoneally for 3 days, group 3 was pretreated with 1 ml/100 g BW of Allium cepa (AcE) for 8 weeks followed by intraperitoneal administration of 0.3 mg/kgBW of CdSO(4) in the last 3 days of experiment, and group 4 was administered 1 ml/100 g BW of AcE throughout the experiment. Testicular weight and semen analysis revealing the sperm count, sperm motility, and sperm morphology was carried out. Superoxide dismutase (SOD), catalase activities, and lipid peroxidation status were also carried out in testes. RESULTS: The study demonstrated that Allium cepa ameliorated CdSO(4)-induced alteration in testicular weight, sperm count, sperm motility, and sperm morphology. It also showed that Allium cepa attenuated the derangement of lipid peroxidation profile in testicular tissues caused by CdSO(4) exposure. CONCLUSIONS: The findings in the study showed that pre-treatment of rat model with Allium cepa extract prevented CdSO(4)-induced reproductive toxicity by improving sperm quality and enhancing testicular lipid peroxidation status.

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents.

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound.

Anti-ulcer & antioxidant activities of Hedranthera barteri {(Hook F.) Pichon} with possible involvement of H+, K+ ATPase inhibitory activity.

BACKGROUND & OBJECTIVE: Hedranthera barteri (HB) is used in folk medicine as a vermifuge, laxative and an anti-inflammatory agent. The aim of this study was to evaluate the anti-ulcer and antioxidant properties of the dichloromethane fraction of HB root (DMHBR). METHODS: Anti-ulcerogenic activity was assessed in cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models in rats and histamine-induced duodenal ulcer (HST) in guinea pigs. The effect of DMHBR (100 mg/kg) on gastric juice for free and total acidity, peptic activity and mucin secretion, using the pylorus ligated model, were evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. The in vitro anti-oxidant assays were explored through DPPH, nitric oxide, hydroxyl radical, superoxide anion scavenging assays. RESULTS: DMHBR reduced the incidence of ulcers in CRU (63.3%), PL (58.5%), ASP (52.7%), HST (75.0%) and AL (53.87%). Also, reductions were observed in the free acidity (49.4%), total acidity (45.8%) and peptic activity (32.9%) with increase in the mucin secretion by 81.6 per cent. DMHBR (60-100 µg/ml) inhibited the H+,K+-ATPase activity with IC50 of 89.64 µg/ml compared with omeprazole (10-50 µg/ml ) with IC50 of 32.26 µg/ml. DMHBR showed antioxidant activity with IC50 values of DPPH (397.69 µg/ml), nitric oxide (475.88 µg/ml), hydroxyl radical (244.22 µg/ml) and superoxide anion radical (285.20 µg/ml). INTERPRETATION & CONCLUSION: DMHBR showed anti-ulcer activity against experimentally-induced peptic ulcer models and exhibited both cytoprotective and anti-secretory property. It exhibited a proton pump inhibition activity and its anti-ulcer properties may be partly ascribed to its antioxidant activities.

Antiulcer and gastric antisecretory effects of Landolphia owariensis extracts in rats.

Water, methanol and chloroform extracts of Landolphia owarensis were investigated for their effects on gastric acid secretion and ulceration in male albino rats. Two models of gastric lesion induced in experimental Wistar rats-HC1/ethanol-induced gastric lesions and Pylorus ligation-induced gastric lesions-were employed. In both models, the antiulcer activity of LA was compared with that of cimetidine (100 mg kg p.o.). In the HCl/Ethanol model, ulcer index and mucus production was determined. In pylorus ligated rat, ulcer index, mucus production, total volume of gastric juice and gastric acidity level were measured. Pre-treatment of animals with the aqueous extracts (100mg/kg and 200mg/kg) orally once daily for two weeks significantly reduced formation of ulcers induced by HCl/ethanol mixture, the percentage inhibition being 43.8 % and 55.27 % respectively. The chloroform extract afforded the least protection with 23.07 % and 14.77 % inhibition. This was also accompanied by significant increases in gastric mucus production. In pylorus ligated rats, total volume of gastric juice and gastric acidity was significantly decreased as compared to control group, to levels comparable to that produced by cimetidine. The results indicate that the leaf extracts of LO contains antiulcer principles.

Studies on the anti-inflammatory and analgesic properties of Tithonia diversifolia leaf extract.

A methanol extract of the dried leaves of Tithonia diversifolia was investigated for anti-inflammatory and analgesic activities. The extract (50-200 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. At the same doses, analgesic effect was also observed with hot plate latency assays maintained at (55 degrees C) as well as on the early and late phases of formalin-induced paw licking in rats. The results of the present study further confirm the use of Tithonia diversifolia traditionally for the treatment of painful inflammatory conditions.