The role of l -arginine/NO/cGMP/K ATP channel pathway in the local antinociceptive effect of berberine in the rat formalin test.

Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30 µ g/paw), l -NAME (NO synthase inhibitor, 10 and 100 µ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 µ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30 µ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0 µ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25 µ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.

Topical Anti-Inflammatory and Analgesic Activities of Citrullus colocynthis Extract Cream in Rats.

Background and objectives:Citrullus colocynthis (CC), known as bitter apple, is used to treat diabetes in Iranian traditional medicine. The aim of this study is to evaluate the anti-inflammatory and analgesic activities of CC cream in rats. Materials and Methods: The carrageenan-induced edema in a rat hind paw was carried out to evaluate the topical anti-inflammatory effect of the CC fruit extract cream (2⁻8%) and the tissue levels of IL-6 and TNF-α were estimated by using a commercial ELISA kit. The topical antinociceptive activity of CC cream (2⁻8%) was evaluated in the rat formalin test. To determine the role of opioid receptors in the local antinociceptive effect of the CC cream, naloxone (20 µg/paw, i.pl.), a non-selective opioid antagonist, was used. Results: The results showed that the CC cream (2⁻8%) dose-dependently reduced the carrageenan-induced paw edema and reversed the changes in the level of TNF-α and IL-6 due to carrageenan-induced edema (p < 0.01). The anti-inflammatory effect of CC cream 8% was comparable to that of hydrocortisone ointment 1%. Furthermore, the application of CC cream (2⁻8%) dose-dependently inhibited both first and second phases of the formalin test (p < 0.05). The antinociceptive effect of the CC cream (8%) was comparable to that of methyl salicylate cream 30%. Moreover, the administration of naloxone significantly reversed the topical antinociceptive effect of the CC cream (p < 0.05). Conclusions: For the first time, this study indicated that the topical application of CC cream possesses significant anti-inflammatory and antinociceptive activities in animal models, which were probably mediated by opioid receptors and the suppression of pro-inflammatory cytokines (TNF-α and IL-6). Thus, the CC cream can be used to treat inflammatory pain and inflammatory diseases.

Carvacrol protects rats against bleomycin-induced lung oxidative stress, inflammation, and fibrosis.

The main objective of this study was to investigate the potential efficacy of carvacrol (CAR) in mitigating bleomycin (BLM)-induced pulmonary fibrosis (PF). Sixty-six male Wistar rats were assigned into two main groups of 7 and 21 days. They were divided into the subgroups of control, BLM, CAR 80 (only for the 21-day group), and CAR treatment groups. The CAR treatment groups received CAR (20, 40, and 80 mg/kg, orally) for 7 or 21 days after an instillation of BLM (5 mg/kg, intratracheally). Results indicated that BLM significantly increased total cell count in bronchoalveolar lavage fluid and the percentages of neutrophils and lymphocytes, and reduced the percentage of macrophages. CAR dose-dependently decreased total cell count and the percentage of neutrophils and lymphocytes. CAR significantly reduced thiobarbituric acid reactive substances and hydroxyproline levels and elevated the total thiol level and catalase, superoxide dismutase, and glutathione peroxidase activities in BLM-exposed rats. Furthermore, CAR decreased the transforming growth factor-ß1, connective transforming growth factor, and tumor necrosis factor-α on days 7 and 21. BLM increased interferon-γ on day 7 but decreased its level on day 21. However, CAR reversed interferon-γ levels on days 7 and 21. Based on histopathological findings, BLM induced inflammation on days 7 and 21, but for induction of fibrosis, 21-day study showed more fibrotic injuries than the 7-day group. CAR showed the improvement of fibrotic injuries. The effect of CAR against BLM-induced pulmonary fibrosis is possibly due to its antioxidant, anti-inflammatory, and antifibrotic activity.

PMSF Attenuates Morphine Antinociceptive Tolerance and Dependence in Mice: Its Association with the Oxidative Stress Suppression.

Opioids use has been limited due to tolerance and dependence as major unwanted effects. Previous evidence has shown that targeting endocannabinoid signaling can prevent the development of opioid tolerance and dependence. This study was designed to evaluate the effect of phenylmethylsulfonyl fluoride (PMSF), an inhibitor of fatty acid amide hydrolase (FAAH), on morphine antinociceptive tolerance and physical dependence in mice. The antinociceptive effects of PMSF at the doses 60, 120, and 300 mg/kg were investigated. Results showed that PMSF has a notable antinociceptive effect at doses 120 and 300 mg/kg. The dose of (60 mg/kg, i.p.) PMSF was considered as a sub-antinociceptive dose. Morphine tolerance and dependence were induced by twice-daily injection of morphine (10 mg/kg, s.c.) for 10 consecutive days and the last dose on day 11. Tolerance was assessed by the hot-plate test and dependence by naloxone-precipitated morphine withdrawal signs. In the brain, oxidative stress markers include activities of glutathione peroxidase, catalase, superoxide dismutase, and levels of malondialdehyde and glutathione were determined. A sub-antinociceptive dose (60 mg/kg) of PMSF could reduce tolerance in both acute and chronic methods of administration. However, alleviation of dependence and suppression of oxidative stress markers occurred in the chronic administration of PMSF. In conclusion, it seems that PMSF can suppress morphine tolerance and dependence. However, more studies are needed to clarify its mechanism.

Synophthalmia in a Holstein cross calf.

Synophthalmia is a form of cyclopia, in which some elements of two eyes are fused and form a single eye in the middle region of the forehead. The head of a Holstein female calf born from a 5-year-old cow was referred to Department of Pathology, School of Veterinary Medicine, Shahrekord University due to multiple congenital anomalies. The calf had been slaughtered immediately after birth due to severe respiratory distress by the owner. The calf showed multiple birth defects, including synophthalmia, holoprosencephaly, absence of optic chiasma, hypoplastic maxilla, curved mandibles, arrhinia and dental pad agenesis. A normal tongue protruded from the defect and small oral cavity. To our knowledge, this particular combination of craniofacial defects has not been previously described in Holstein calf.

A report on the genital myiasis by Wohlfahrtia magnifica in camel herds in southwest of Iran.

Myiasis is a disease of vertebrate animals caused by different fly larvae. Wohlfahrtia magnifica is responsible for serious losses in animal husbandry in Eurasia. Larvae of W. magnifica parasitize several warm-blooded vertebrates and are responsible for a severe traumatic myiasis of mucosal membranes or wounds. This myiasis has been reported in many European areas, but for the first time was reported from Iran. Larvae infestation was observed in five camels out of 35 (14.28%) around the perinea and vaginal region of camels in a herd in southwest of Iran. The larvae samples were collected and transferred to the laboratory of parasitology for identification. This is the first report of infestation of a camel herd (camelus dromedarius) in Iran. The treatment was performed and prevented the loss from camels and improved their physical condition. Although the myiasis is not a lethal disorder, however knowledge of the disease is necessary from preventive, diagnostic and curative standpoint.