Myrtenol Protects Against Acute Kidney Injury Induced by Cisplatin in Mice

Background and objectives: Cisplatin is an effective anticancer drug which has some side effects such as acute kidney injury. Myrtenol, a monoterpene alcohol which is found in some plants, has various pharmacological effects including anti-inflammatory and antioxidant activities. In this study, we evaluated the nephroprotective effects of myrtenol in acute kidney injury induced by cisplatin in male mice. Methods: In this experimental in-vivo study, 35 male mice were randomly separated into 5 groups, including control, CIS (20 mg/kg cisplatin, intraperitoneally on day 1), dimethyl sulfoxide (DMSO; received cisplatin only on day 1, plus DMSO 1% on the first day, continued for 3 days), and treatment groups (received cisplatin only on day 1, plus myrtenol 25 mg/kg and 50 mg/kg intraperitoneally on the first day, continued for 3 days). The blood urea nitrogen (BUN) levels were evaluated in serum. The renal tissues were collected for evaluating malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities; histopathological investigation was also performed. Results: Our results showed that cisplatin administration caused significant elevation in the levels of renal MDA and serum BUN; in contrast, renal SOD and CAT activities significantly reduced. Myrtenol treatment, especially 50 mg/kg for four consecutive days mitigated these alternations in serum and renal tissue. Also, the kidney’s histopathological investigations were consistent with biochemical and oxidative parameters. Conclusion: The results of our study revealed that myrtenol ameliorates acute kidney injury induced by cisplatin via oxidative stress suppression

Sumatriptan effects on morphine-induced antinociceptive tolerance and physical dependence: The role of nitric oxide

Sumatriptan, a 5HT (5-hydroxytryptamine)1B/1D receptor agonist, showed neuroprotection in different studies. The aim of the present study was to investigate the effect of sumatriptan on morphine-induced antinociceptive tolerance and physical dependence. We also investigated the possible role of nitric oxide (NO) on sumatriptan effects. Tolerance was induced by morphine injection (50, 50, 75 mg/kg) three times daily for five days. Antinociceptive latency after acute and chronic treatment with sumatriptan (0.001, 0.01, 0.1 and 1 mg/kg) was measured by hot plate test in morphine-dependent animals. To investigate the possible involvement of NO, different isoforms of nitric oxide synthase (NOS) inhibitors including L-NAME, aminoguanidine and 7-nitroindazole were co-administered with sumatriptan. Nitrite level in mice hippocampus was quantified by Griess method. To examine the role of sumatriptan on physical dependence, three parameters of withdrawal signs were recorded after injection of naloxone (4 mg/kg). Acute treatment with sumatriptan (0.01, 0.1 and 1 mg/kg) attenuated the antinociceptive tolerance (P < 0.001). Chronic injection of sumatriptan (0.001, 0.01 and 0.1 mg/kg), as well, decreased the antinociceptive tolerance (P < 0.001). Moreover, co-administration of NOS inhibitors prevented the effects of sumatriptan. Sumatriptan significantly increased the level of nitrite only after chronic administration. Sumatriptan administration showed no alteration in naloxone-precipitated withdrawal signs. Acute and chronic administration of sumatriptan attenuated morphine antinociceptive tolerance; at least in chronic phase via nitrergic pathway. Our data did not support beneficial effects of sumatriptan on morphineinduced physical dependence in mice

Bio-effectiveness of the main flavonoids of Achillea millefolium in the pathophysiology of neurodegenerative disorders- a review

The Achillea millefolium L. (Yarrow) is a common herb which is widely being used, worldwide. Achillea is being used for treatment of many disorders since centuries. It is considered safe for supplemental use and flavonoids such as kaempferol, luteolin and apigenin are of main constituents present in Achillea. Most of both antioxidant and anti-inflammatory properties of this herb have been attributed to its flavonoid content. Oxidative and inflammatory processes play important roles in pathogenesis of neurodegenerative diseases. Present review was aimed to review the latest literature evidences regarding application of Achillea and/or its three main flavonoid constituents on epilepsy, Alzheimer's disease, multiple sclerosis, Parkinson's disease and stroke

Sumatriptan ameliorates renal injury induced by cisplatin in mice

Objective(s): Cisplatin (Cis) is an anticancer compound, which is used for the treatment of various cancers. Sumatriptan (Suma) is a selective agonist of 5-hydroxytryptamine 1B/1D (5HT1B/1D) receptor, which is prescribed for the management of migraine. It is well-established that Suma has anti-inflammatory and antioxidant properties. We have explored the protective effects of Suma in the mitigation of Cis-induced nephrotoxicity. Materials and Methods: The mice received a single IP injection of Cis (20 mg/kg) on the first day of the experiment. Suma treatment (0.1 and 0.3 mg/kg/day, IP) was started on day 1 and continued for 3 consecutive days. Results: Creatinine (Cr), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels were elevated and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) activities were decreased in Cis-treated mice. Suma (more potently 0.3 mg/kg) reduced Cr, BUN and MDA levels and increased SOD and GPx levels. Suma also reduced the acute renal injury (tubular degeneration, tubular cells vacuolation, tubular necrosis and cast), which corresponded to kidney damage in Cis-treated mice. Conclusion: These findings demonstrate that Suma mitigates Cis-induced renal injury by inhibition of oxidative stress and enhancing the antioxidant enzymes activities

TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke

Investigate the effect of metformin on some of the behavioral indicators in ovariectomized middle aged mice

Introduction: Aging process is inevitable, which increases the risk of illness and death in people. Menopause occurs as a part of the aging process. The aim of this study was to evaluate the effect of metformin (Met) on muscle strength, anxiety and memory in ovariectomized mice Methods: Thiswas an experimental study.  96 female mice (Age 6 months) (20-25 g) were randomly divided into sex groups, including: (1) sham, (2) ovariectomized, (3 and 4) ovariectomized + Met (1 and 10 mg/kg) (5) Met 10 mg/kg, and (6) healthy. At first, the mice were ovariectomized and then received Met for six months. Muscle strength, memory, and anxiety in the exprimental groups was examined. Statistical analysis was performed via SPSS16 and the differences between groups were analyzed by one way ANOVA. Results: The results of the study showed Met with doses of 1 mg / kg and 10 mg significantly reduced the  anxiety of mice (p = 0.0295 and p = 0.0024, respectively), increased memory (p = 0.0004 and p = 0.0044, respectively) and at dose of 10 mg / kg it improved muscle strength (p = 0.0148) compared to the ovariectomy group. Conclusion: Metformin  has beneficial effects on behavioural manifestations of aging and ovarectom

The effect of head cooling and remote ischemic conditioning on patients with traumatic brain injury

Summary: Cerebral impairment caused by an external force to the head is known as traumatic brain injury (TBI). The aim of this study was to determine the role of local hypothermia and remote ischemic conditioning (RIC) on oxidative stress, inflammatory response after TBI, and other involved variables. The present study is a clinical trial on 84 patients with TBI who were divided into 4 groups. The head cooling for 1.5 to 6 hr was performed in the first three days after TBI. RIC intervention was performed within the golden time after TBI in the form of four 5-min cycles with full cuff and 5 min of emptying of cuff. The group receiving the head cooling technique recovered better than the group receiving the RIC technique. Generally, combination of the two interventions of head cooling and RIC techniques is more effective on the improvement of clinical status of patients than each separate technique

Protective effect of metformin on D-galactose-induced aging model in mice

Objective(s): Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via improving glucose utilization and reducing the gluconeogenesis. Met has been shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The present study investigated the possible effect of Met on the D-galactose (D-gal)-induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for six weeks. Anxiety-like behavior, cognitive function, and physical power were evaluated by the elevated plus-maze, novel object recognition task (NORT), and forced swimming capacity test, respectively. The brains were analyzed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met treated mice showed significantly improved learning and memory ability in NORT compared to the D-gal-treated mice. Furthermore, Met increased the physical power as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion: Our results suggest that the use of Met can be an effective strategy for prevention and treatment of D-gal-induced aging in animal models. This effect seems to be mediated by attenuation of oxidative stress and enhancement of the neurotrophic factors

Modulatory Effects of Memantine on Neuronal Response Properties in Rat Barrel Cortex

Introduction: Memantine as N-Methyl-D-Aspartic Acid (NMDA) receptor antagonist is used in some neurological disorders. Moreover, memantine presents modulatory effects on the somatosensory information processing in healthy subjects. This study investigated the effects of memantine on electrophysiological properties of barrel cortex neurons in male rats.  Methods: Single unit recording was used to evaluate the electrophysiological properties of barrel cortex neurons. The neural responses to the Principal Whisker (PW), Adjacent Whisker (AW), and combined displacement of two whiskers [20 ms Inter-Stimulus Intervals (ISIs)] were recorded before and 2 hours after memantine gavage (10 mg/kg). A Condition Test Ratio (CTR) was calculated for assessing inhibitory interactions.  Results: Two hours after memantine gavage, neuronal ON and OFF responses to PW deflection were decreased. Furthermore, CTR for both ON and OFF responses was decreased following memantine administration.  Conclusion: The current study demonstrated that memantine modified neural response properties in the rat barrel cortex