Journal of Basic & Clinical Pathophysiology
Volume:9 Issue: 1, Winter-Spring 2021

This study aimed to determine anti-depressant effect of hesperidin in ovariectomized mice and its possible interaction with dopaminergic and serotoninergic systems.

In experiment 1, mice were kept as control and sham groups, ovariectomized (OVX), OVX+ hesperidin (12.5 mg/kg), OVX+ hesperidin (25 mg/kg) and OVX+hesperidin (50 mg/kg). In experiment 2, mice were kept as control and sham, OVX, OVX+hesperidin (50 mg/kg), OVX+dopamine (25 mg/kg) and OVX+co-injection of hesperidin and dopamine. Experiments 3-5 were like experiment 2, except 6-OHDA (dopamine inhibitor, 100 mg/kg), fluoxetine (selective serotonin reuptake inhibitor, 5 mg/kg) and cyproheptadine (serotonergic receptor antagonist, 4 mg/kg) was injected instead of dopamine. Then, forced swimming test (FST), tail suspension test (TST) and open field test (OFT) were done. Also, serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) levels were determined.

According to the results, OVX increased immobility time in FST and TST tests as compared to control group (P<0.05). Hesperidin (50 mg/kg) decreased immobility time as compared to OVX group (P<0.05). Co-injection of hesperidin+dopamine decreased immobility time in TST and FST and increased number of crossing in OFT (P<0.05). Co-injection of hesperidin+6-OHDA significantly decreased antidepressant activity of the hesperidin on immobility time and decreased positive effect of the hesperidin on the number of crossing (P<0.05). Co-injection of hesperidin+Fluoxetine significantly amplified antidepressant activity of the hesperidin on immobility time and number of crossing (P<0.05). Co-injection of hesperidin+cyproheptadine decreased antidepressant activity of hesperidin on immobility time (P<0.05). Hesperidin (12.5, 25 and 50 mg/kg) decreased the MDA, while increased SOD and GPx levels in OVX mice (P<0.05).

It is assumed that antidepressant activity of hesperidin is mediated via dopaminergic and serotoninergic receptors in OVX mice.

Heart rate variability (HRV) is the amount of heart rate fluctuations around the mean heart rate and can be used as a mirror of the cardiorespiratory control system. It is a valuable tool to investigate the sympathetic and parasympathetic functions of the autonomic nervous system. This variation during respiration is called respiratory sinus arrhythmia (RSA). RSA reflects heart rate control system, especially a cardiac parasympathetic activity which can be evaluated by some proper tests such as standing test. Researches show HRV alters among patients with coronary artery diseases (CAD).

In this study, we intended to calculate amount of HRV in patients with chest pain before diagnostic exercise stress test (EST) and to compare the obtained results with EST results. 66 (19 women and 47 men) with chest pain. Volunteers and unknown CAD referred for EST with a mean age of 50 years were participated in this study. Each volunteer underwent deep breathing (6 breaths/minute) and standing up tests prior to EST for HRV measurements.

There was less variation in heart rate during both deep breathing and standing up tests in patients with positive result of EST than in patients with negative result of EST.

Our study suggests that HRV is depressed in individuals who have unknown coronary artery disease with an immediate positive EST result.

Ornithogalum cuspidatum is a medicinal plant in Iranian traditional medicine that has several pharmacological effects. Due to strong antioxidant and anti-inflammatory activities of this plant, the current study was designed to evaluate wound healing activity of O. cuspidatum on cutaneous wounds in Wistar rats.

A full-thickness excisional wounds was induced on the back of 50 Wistar rats. The animals were randomly divided into five groups, including control, basal cream, phenytoin, O. cuspidatum 5%, and O. cuspidatum 10%. Five animals of each group were euthanized at 10 and 20 days post-injury (DPI) and wounds were assessed through gross and histopathological analyses. Also, hydroxyproline content and MDA, NO and TOS concentrations were determined.

Treated animals with O. cuspidatum showed a significant reduction in the wound surface area at 10 and 20 dpi. Moreover, treatment with this plant reduced the number of lymphocytes and macrophages, increased the number of fibroblasts at the earlier stages and enhanced number of fibrocytes at the later stages of wound healing. O. cuspidatum significantly improved re-epithelialization and epithelial formation, enhanced hydroxyproline content and thereby maturity of the collagen fibers. Also, O. cuspidatum significantly reduced MDA, NO and TOS concentration as oxidant status in granulation tissue.

The present study demonstrated that application of hydroethanolic extract of O. cuspidatum promoted wound healing due to increased re-epithelialization and collagen deposition in wound tissue and also induction of considerable wound contraction, so it can be considered as a therapeutic agent for wound healing.

Type 2 diabetes is a global concern worldwide. Despite extensive studies on the physiological effects of diabetes on the testicular functions, the impact of testosterone deficiency on the glucose homeostasis remains to be clarified. This study was designed to investigate the effects of testosterone deprivation and its replacement with testosterone enanthate on the molecular mechanisms of insulin signaling pathway in the liver of rats.

We first established a rat model of testosterone deficiency by castration (CAS-S). Subsequently, the castrated rats were administrated by subcutaneous injection of testosterone (CAS-T). Thereafter, fasting blood glucose (FBG), insulin, and homeostasis model-insulin resistance (HOMA-IR) level was assessed. The testosterone and insulin levels were further analyzed by ELISA. The mRNA expression of insulin receptor (IR)-β, insulin receptor-substrate (IRS)1 and 2 as well as glucose transporter (GLUT) 2 in the liver was analyzed by q-RT-PCR assay.

Our data showed that testosterone deprivation significantly increases FBG and HOMA-IR and down-regulates IRS-1 and IRS-2 mRNA expression in the liver. However, the mRNA expression of GLUT2 and IR-β was not affected. We also found that testosterone administration could improve the liver insulin resistance.

These findings suggested that testosterone deprivation can impact insulin signaling in the liver via suppressing expression of IRS-1 and IRS-2 mRNA and treatment with testosterone can improve the insulin resistance in the castrated rats. Further experimental and clinical pathways are needed to be assessed for clinical application of our finding.

Menopause in women is associated with many complications that most of them are related to the decrease of estrogen levels in this period. Treatment with high doses of estrogen is common but has side effects. In this study, the effect of l-arginine administration on the level of this hormone in elderly rats was investigated.

Elderly Wistar rats were first studied with the help of Papanicolaou test to identify the stage of female sexual cycle. If confirmed to have diestrus phase, the rats were randomly classified into the following groups: control (saline 1 ml/kg, i.p.) and l-arginine group (5, 25, and 50 mg/kg). They were injected saline or l-arginine over a period of three to nine days. At the end, the rats were anesthetized by an i.p. injection of ketamine 100 mg/kg and xylazine 20 mg/kg and the blood samples were collected and the estrogen levels were measured with ELISA kit. The rats’ ovaries and uteri were also biometrically examined and fixed in the formalin. They were stained by H&E method and the number of cysts in the ovaries were counted. Data were analyzed by the ANOVA.

L-arginine at all doses (5-50 mg/kg) during all injection periods from three to nine days significantly increased the estrogen levels, but prominently reduced the ovarian cysts at the lowest dose (5 mg/kg).

Low doses of l-arginine over short periods of time can relieve menopausal problems including estrogen levels and ovarian status, probably by the modulator nitric oxide.

Colchicine is a neurotoxin substance. Its intraventricular injection causes oxidative stress, inflammation, destruction of cholinergic and glutaminergic neurons and consequently impairs memory and learning. Crocin is an effective ingredient in saffron that has antioxidant and anti-inflammatory potential with beneficial effects on memory and learning. This study investigated the effect of crocin on lipid peroxidation and histological changes of the hippocampus following intracerebroventricular injection of colchicine in the rat.

40 male rats were randomly divided into 5 groups as follows: 1-Sham, 2- Sham + crocin at a dose of 50 mg/kg, 3- Colchicine, 4- Colchicine + crocin at a dose of 10 mg/kg, and 5- Colchicine + crocin at a dose of 50 mg/kg. Cognitive disorder was induced by injection of colchicine bilaterally into the brain ventricles through stereotaxic surgery. Crocin was daily administered 2 days before surgery till day 7 after the surgery. In the third week after the surgery, malondialdehyde (MDA) was evaluated in hippocampal homogenate. The number of neurons was also studied by Nissl staining in CA1 and CA3 regions.

The results showed that crocin treatment at a dose of 50 mg/kg significantly reduced MDA. Histopathological assessment did not show significant changes regarding neuronal number.

The findings of this study indicate the dose-dependent effect of crocin in reduction of hippocampal MDA following intracerebroventricular injection of colchicine in the rat. However, it is not effective regarding number of hippocampal pyramidal neurons after colchicine challenge.

Mosquito is a vector of several life threatening diseases affecting humans. The use of synthetic insecticides in the vector control is not advisable due to concern about environmental sustainability, harmful effect on human health and increasing insecticide resistance. So, the objective of this study was to assess larvicidal activity of essential oils (EOs) of Zataria multiflora, Eucalyptus caesia Benth, and Mentha piperita against the Culex mosquito.

The larvicidal activity of the essential oils were tested according to the WHO procedure. The larvae exposed to three-fold serial dilution of oils (2.5-400 ppm) using a dipping method for 24 h and then simultaneously each replicate was incubated in separate petri dishes at 27°C and 80-90% relative humidity. Mortality rate was recorded after an exposure of 24 h. LC50 and LC90 were calculated using Probit analysis and all data were analyzed using ANOVA and post hoc Tukey test.

In the comparative analysis of the essential oils, LC50 & LC90 of Z. multiflora, E. caesia Benth and M. piperita were5.09429 and26.9919, 3.66376 and 35.3173, and 8.3115 and 218.888 ppm, respectively. Also, as the concentration of essential oil increased, mortality rate of larvae increased too.

This study concluded that the essential oils of Z. multiflora, E. caesia Benth and M. piperita have appropriate larvicidal activity against Culex, therefore, they can be used as good alternative to the Culex biological control.

Injection of l-arginine, a precursor of nitric oxide, in the rat’s hippocampus or periaqueductal gray matter reduces the analgesic effect of morphine on formalin-induced pain, but the effect of simultaneous injection of the substance in both areas have not been shown as our purpose of this research.

Wistar rats were used as control, morphine, and l-arginine groups. The rats were simultaneously cannulated in two areas of the dorsal hippocampus and laterodorsal PAG. One week later, the control animals received 50 μl of 2.5% formalin in the paw of the left foot under restrainer. The morphine group 10 min before formalin received the opioid (6 mg/kg, intraperitoneally). Other groups took l-arginine (0.25-2 µg/rat) in only one area (d hippocampus or ld PAG), prior to morphine administration. The effective dose of l-arginine (0.5 µg/rat) simultaneously was injected in both areas. The findings were analyzed by analysis of variance (ANOVA) under α=0.05.

Morphine induced analgesic response. Injection of NO precursor both separately and simultaneously in the two nuclei reduced morphine-induced analgesia.

Increasing levels of NO due to exclusive or concurrent injection of l-arginine in the areas likely antagonize the morphine response.