Evaluation of the serum levels of CCL2, CCL3, and IL-29 after first and second administrations of the COVID-19 vaccine (Oxford-AstraZeneca).

BACKGROUND: Previous studies show that chemokines and cytokines play a very important role in eliciting an appropriate response against viruses. Vaccination causes inflammation in the person receiving the vaccine, accompanied with production of inflammatory molecules by immune cells. The more and better the production and expression of chemokines and cytokines by immune cells, the better the response of the acquired immune system. Chemokines and cytokines are critical in promoting the innate immune response against the COVID-19. Here we intended to assess serum levels of CCL2, CCL3, and interleukin (IL)-29 in patients received COVID-19 vaccine. METHODS: In this study, 40 subjects vaccinated with the Oxford-AstraZeneca COVID-19 vaccine were selected. Blood samples were collected before injection of the vaccine, 3-5 days after the first dose injection, and 3-5 days subsequent to the second vaccination. To check the serum level of CCL2, CCL3, and IL-29, ELISA technique was used. RESULTS: Our results indicated that the serum levels of CCL2, CCL3, and IL-29 were significantly higher after first and second dose of vaccination compared to before vaccine administration. Furthermore, serum levels of all these mediators were higher after second dose of vaccine compared to the first vaccine administration. CONCLUSIONS: Oxford-AstraZeneca COVID-19 vaccine is able to induce inflammatory CCL2 and CCL3 chemokines as well as protective interferon lambda (IL-29).

Calcium Dobesilate Ameliorates Cisplatin-induced Hepatotoxicity by Inhibiting Liver Oxidative Stress in Mice.

Background: Cisplatin has potent antitumor properties. It has several toxic side effects, such as hepatotoxicity. It is thought that hepatotoxicity induced by cisplatin is caused by oxidative stress. Objectives: It has shown that calcium dobesilate (CD) has potent antioxidant properties. The present study aimed to assess CD protective effects on cisplatin-induced hepatotoxicity in mice. Methods: In this study, 28 mice were selected randomly and were divided into four groups, including control, cisplatin (20 mg/kg, i.p., only on the first day of the experiment), Cisplatin+CD 50 (50 mg/kg CD, orally), and Cisplatin+CD 100 (cisplatin with 100 mg/kg CD, orally). A 4-day oral gavage of CD was applied to the treated groups. The mice were sacrificed on the 5th day, and serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), malondialdehyde (MDA) and reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme activity levels in liver tissue were evaluated. Histopathological evaluation was assessed using hematoxylin and eosin-stained liver tissue sections. Results: The results indicated that there was a significant increase in GSPT, SGOT, ALP, and MDA and also a significant reduction in the liver activity of SOD and GPx in cisplatin-treated animals. Treatment with CD (100 mg/kg) remarkably attenuated the GSPT, SGOT, ALP, MDA, and ROS levels. Moreover, CD (100 mg/kg) elevated the SOD and GPx activity in the liver tissue of cisplatin-treated mice. Conclusions: The findings showed that CD has a protective effect against cisplatin-induced hepatotoxicity, at least by improving the antioxidant parameters.

Distinct signatures on d-galactose-induced aging and preventive/protective potency of two low-dose vitamin D supplementation regimens on working memory, muscular damage, cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation.

Chronic administration of d-galactose (d-gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d-gal-induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre-induction and simultaneous, respectively) in two vital organs (heart and brain). d-gal-induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre-induction schedule prevented d-gal-induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d-gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

The protective effects of hyperoxic pre-treatment in human-derived adipose tissue mesenchymal stem cells against in vitro oxidative stress and a rat model of renal ischaemia-reperfusion.

Objective: Improvement of cell survival is essential for achieving better clinical outcomes in stem cell therapy. We investigated the effects of hyperoxic pre-treatment (HP) on the viability of human adipose stromal stem cells (ASCs).Materials and Methods: MTT and Western blot tests were used to assess cell viability and the expression of apoptosis-related proteins, respectively. For the in-vivo trial, the rats were subjected to renal ischaemia-reperfusion (IR).Results: The results showed that HP could significantly increase the viability of ASCs and decrease apoptotic markers (Bax/BCL-2 ratio and Caspase-3) compared with control cells. There were some additional effects with regard to the improvement of renal structure and function in the animal model. However, the difference between the treated and non-treated transplanted ASCs failed to reach significance.Conclusion: These results suggested that HP could increase the survival of ASCs against oxidative stress-induced damages in the in-vitro condition, but this strategy was not highly effective in renal IR.

Anti-obesity effects of aerobic exercise along with Rosa canina seed extract supplementation in rats: The role of irisin and adipolin.

Aerobic exercise and some bioactive compounds in medicinal plants have anti-obesity effects and can suppress body weight. The aim of this study was to determine the anti-obesity effects of 6 weeks of aerobic exercise (AE) and supplementation of the hydroalcoholic extract of Rosa canina fruit seed (RC) in obese male rats. In this experimental study, 24 high-fat diet (HFD) obese male Wistar rats were used. The animals were randomly divided into 4 groups (6 rat in group), including 1. HFD (the control group), 2. HFD + AE, 3. HFD + RC and 4. HFD + AE + RC. An obesity protocol was implemented for 12 weeks with the consumption of HFD along with the consumption of water containing 1 % fructose. Afterwards, the animals were given access only to HFD food until the end of the study in all the groups. After the obesity protocol, 6 weeks of exercise (50-70 % VO2 max) and access to the extract (1 % of the consumed food) were given. Bodyweight, subcutaneous adipose tissue mass, and some serum lipid profiles were measured in the experimental groups. The serum levels of irisin and adipolin were evaluated by the ELISA method. Expression of FNDC5 and CTRP12 in adipose tissue were determined by real-time PCR. The findings of this study showed that body weight (P = 0.001), subcutaneous adipose tissue mass (P = 0.001), and lipid profile were significantly reduced in HFD + AE and HFD + AE + RC groups compared with the HFD group. Irisin was significantly increased in the HFD + AE and HFD + AE + RC groups compared with the HFD group (P = 0.019 and P = 0.001; respectively) and in the HFD + AE + RC group compared with the HFD + RC group (P = 0.004). Moreover, adipolin, expression of FNDC5 and CTRP12 were significantly increased in the HFD + AE + RC group compared with the HFD group (P = 0.004, P = 0.023, and P = 0.001; respectively). Altogether, HFD + AE with HFD + RC diet supplementation could reduce weight and the risks of obesity, at least, through the up-regulation of irisin and adipolin.

Anti-tumor effects of Thymus Caramanicus Jalas extract in mice through oxidative stress, inflammation and apoptosis.

OBJECTIVE: Breast cancer causes death in women. Thymus Caramanicus Jalas (TCJ) as a polyphenolic plant has an antiproliferative effect. Accordingly, this investigation studied the TCJ extract anti-tumor effects in a breast cancer model. METHODS: Twenty-four female BALB/c mice were used in 4 groups including (1) breast cancer (control); (2), (3) and (4) breast cancer + 100, 300 and 500 mg/kg of TCJ extract (once daily for 20-days after breast tumor induction). The breast tumour was induced by 4T1 cell carcinoma injection. Then tumor size and weight were measured. Tumor necrosis factor-α (TNF-α), nuclear factor κ-B (NF-κB), interleukin-6 (IL-6) as inflammatory markers and also Bcl-2, Bax, cytosolic cytochrome-c, apoptosis-inducing factor, and cleaved caspase-3 as biochemical apoptosis markers were evaluated in tumor tissue with western blotting analysis. Also, malondialdehyde (MDA) concentration, hydrogen peroxidase (H2O2), catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were exanimated. KEY FINDINGS: Treatment with TCJ extract (500 mg/kg) decreased the tumor volume, tumor weight, GPx, SOD, and catalase enzyme activity versus the control group (P < 0.05). Also, TCJ (500 mg/kg) extract increased MDA, H2O2, inflammatory and apoptosis markers versus control (P < 0.05). CONCLUSIONS: Current study showed that TCJ can induce anti-tumour effects via promoting inflammation, apoptosis, and oxidative stress in breast tumour tissue.

Neuroprotective effect of Achillea millefolium aqueous extract against oxidative stress and apoptosis induced by chronic morphine in rat hippocampal CA1 neurons.

Chronic opioid abuse can impair the hippocampal region of the brain. This study evaluates the neuroprotective effect of Achillea millefolium (Ach) on chronic morphine­induced learning and memory impairment, oxidative stress, and neuronal apoptosis in the CA1 region of the rat hippocampus. Thirty­two male Wistar rat rats were classified into four treatment groups (n=8). Morphine sulfate was administered chronically. The treatment groups were given Ach aqueous extract (100, 250, and 500 mg/kg), orally, each day. After 28 days, the Morris water maze test was performed on all subjects. Caspase­3, Bax, and Bcl­2 proteins expression in the CA1 region of hippocampal tissue was analyzed using the western blot method. Also, malondialdehyde concentration, glutathione peroxidase activity, and superoxide dismutase activity were evaluated. The results indicated that Ach extract can improve spatial learning and memory defects in morphine­treated rats. Ach administration also ameliorated apoptosis and oxidative stress indicator levels in hippocampal CA1 of morphine­treated animals. Based on the present study, Ach improved spatial learning and memory defects, and reduced oxidative stress and apoptosis in the hippocampus CA1 region, in chronic morphine­treated animals.

Calcium dobesilate ameliorates hepatorenal injury induced by carbon tetrachloride in mice.

Objectives: Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method. Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P<0.05). However, CaD (100 mg/kg) could significantly improve the histopathological change in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). In addition, CaD (100 mg/kg) attenuated the pro and anti-apoptotic markers in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). Conclusion: CaD (100 mg/kg) has a protective effect against hepatorenal injury induced by CCl4 at least via its anti-apoptotic and anti-oxidant properties.

Chronic treatment with coenzyme Q10 mitigates the behavioral dysfunction of global cerebral ischemia/reperfusion injury in rats.

Objectives: The Ischemia/reperfusion (I/R) phenomenon has a critical role in brain injuries induced by some kinds of stroke. The current study investigates the effects of Coenzyme Q10 (Q10) on global cerebral I/R in rats. Materials and Methods: Fifty male Wistar rats were used in this study. The global cerebral I/R was induced by obstructing both common carotid arteries for 20 min and the animals were treated with Q10 (200 mg/kg; PO.) for 6 weeks. Depressive and anxiety-like behaviors were assessed using the elevated plus-maze and forced swimming test, respectively. Working and spatial learning and memory were assessed by the Y-maze continuous alternation task and Morris water maze. The brain tissues were evaluated for brain edema, brain-derived neurotrophic factor (BDNF) levels, and superoxide dismutase (SOD) activities. Results: Our results indicated that global cerebral I/R increased anxiety and depression-like behavior as well as reduced cognitive performance. Moreover, the levels of BDNF and activities of SOD are reduced in stroke animals. Chronic post-stroke treatment with Q10 decreased brain edema. Furthermore, Q10 administration reduced anxiety and depressive-like behavior as well as cognitive impairments in stroke animals. Q10 also increased the SOD activities and BDNF levels in the brain tissues of stroke animals. Conclusion: Finally, we can conclude that using Q10 supplementation may be beneficial against the global cerebral I/R complications.

Calcium dobesilate protects against d-galactose-induced hepatic and renal dysfunction, oxidative stress, and pathological damage.

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

Gemfibrozil, a lipid-lowering drug, reduces anxiety, enhances memory, and improves brain oxidative stress in d-galactose-induced aging mice.

Gemfibrozil (GFZ) is a lipid-lowering drug with several other effects, such as antioxidant and anti-inflammatory activities. In the current study, chronic d-galactose treatment (d-gal, 150 mg/kg/day; i.p., 6 weeks) induced a model of accelerated aging in male mice and was used to study the behavioral, anti-oxidative, and neuroprotective effects of GFZ (100 mg/kg/day; p.o.). Anxiety-like behaviors were assessed using the elevated plus-maze while working memory was measured by spontaneous alternation in a Y-maze. Brain oxidative stress was determined by measuring malondialdehyde (MDA) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Neuropathological evaluation of the brain with hematoxylin-eosin and Masson's trichrome staining was also performed. The results demonstrated that the anxious-like phenotype and the cognitive impairments observed in d-gal-treated mice could be prevented in those animals coadministered with GFZ. Besides, the decrease in SOD and GPx antioxidant enzymatic activities and increase of MDA levels were also prevented in the brains of d-gal plus GFZ treated mice. Preliminary hematoxylin-eosin staining also suggested neuroprotective effects of GFZ. The results of Masson's trichrome staining showed no evidence of fibrosis in brain sections of different experimental groups. The current data provide novel insights into GFZ in the d-galactose-induced aging mouse model that open promising future research lines to determine inflammatory mediators and cell signaling underlying these effects.

The protective effect of carvacrol on acetaminophen-induced renal damage in male rats.

BACKGROUND: Acetaminophen overdose causes renal injury via oxidative stress and apoptosis induction. Carvacrol has several pharmacological properties such as antioxidant, anti-inflammation and anti-apoptotic effect. The aim of this study was to determine the protective effect of carvacrol on acetaminophen-induced renal damage in rats. METHODS AND RESULTS: Forty male Wistar rats were randomly divided to five groups (n = 8) including control, carvacrol 10 mg/kg, acetaminophen, acetaminophen + carvacrol 5 mg/kg, and acetaminophen + carvacrol 10 mg/kg. Animals received a single dose of acetaminophen (500 mg/kg), then were treated with carvacrol for 1 week (daily). Afterwards, renal blood flow (RBF), mean arterial pressure, renal perfusion pressure, renal vascular resistance (RVR), blood urea nitrogen (BUN), and serum creatinine were measured. Also, malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured in the kidney tissue. Hematoxylin and eosin method was used for histological assessment. The Western blotting analysis was used to determine the Bax, Bcl-2 and cleaved caspase-3 proteins expression level in the kidney tissue. Carvacrol (10 mg/kg) significantly increased the RBF, GPx and SOD activities and also reduced the RVR, serum creatinine, BUN, and MDA in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05). Also, carvacrol significantly decreased the cleaved caspase-3, Bax proteins expression level, and kidney tissue damage score in the acetaminophen + carvacrol 10 mg/kg group versus acetaminophen group (P < 0.05). CONCLUSIONS: This study showed that carvacrol can attenuate the acetaminophen induced acute kidney damage via suppressing oxidative stress and apoptosis biochemical factors.

Involvement of T-type calcium channels in the mechanism of low dose morphine-induced hyperalgesia in adult male rats.

It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 µg i.t. and 1 µg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 µg i.t.) and mibefradil (2.5 and 5 µg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 µg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats.

Effects of valsartan on morphine tolerance and dependence in rats.

BACKGROUND AND PURPOSE: Opiates are traditionally used for the treatment of pain. Chronic consumption of opiates such as morphine (MOR) induces tolerance and dependence. This study aimed to investigate the effects of valsartan (VAL), as an angiotensin II receptor blocker, on the induction and expression of MOR analgesic tolerance and physical dependence in rats. EXPERIMENTAL APPROACH: MOR 10 mg/kg was injected s.c. twice a day for 7 days to induce tolerance and dependence. For evaluating the effect of VAL on the induction of MOR analgesic tolerance and physical dependence, 20 mg/kg VAL was administered orally (once a day) during the 7 days of the examination period. The tail-flick test was performed every day. On day 7, 5 mg/kg naloxone () was injected s.c. into the morphine-dependent rats and the rats were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. For evaluating the effect of VAL on the expression of MOR-analgesic tolerance and physical dependence, 45 min before the last MOR injection, VAL was administered only on day 7. The tail-flick test was performed and naloxone was injected into the addicted rats and they were monitored for 30 min for the frequency of withdrawal signs such as jumping, diarrhea, defecation, head tremor, rearing, scratching, sniffing, teeth chattering, and wet-dog shake. FINDINGS/RESULTS: Our results revealed that the co-administration of VAL with MOR for 7 consecutive days reduced the induction of MOR tolerance. Moreover, VAL administration for 7 days along with MOR reduced the frequency of diarrhea and defecation in naloxone-injected animals. CONCLUSION AND IMPLICATIONS: According to the results presented in this study, chronic administration of VAL prevented the induction of MOR-analgesic tolerance and dependence in rats.

Calcium Dobesilate Reverses Cognitive Deficits and Anxiety-Like Behaviors in the D-Galactose-Induced Aging Mouse Model through Modulation of Oxidative Stress.

The long-term treatment of mice with D-galactose (D-gal) induces the overproduction of reactive oxygen species (ROS) and is a well-accepted experimental model of oxidative stress-linked cognitive disorders in physiological aging. Calcium dobesilate (CaD, Doxium®) is an established vasoactive and angioprotective drug commonly used for the clinical treatment of diabetic retinopathy and chronic venous insufficiency. It has antioxidant properties and controls vascular permeability. In the current study, we evaluated the protective effects of CaD (50 and 100 mg/kg/day p.o.) in male mice treated with D-gal (500 mg/kg/day p.o.) for six weeks. Results demonstrated that body weight loss, anxiety-like and cognitive impairments of D-gal-treated animals were reversed by CaD administration as evaluated by the measurement of mice performance in elevated plus-maze, Y-maze, and shuttle box tests. CaD treatment also inhibited the oxidative stress in aging mouse brains by decreasing malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) enzyme activities. These results could open new perspectives for the clinical use of CaD in treating and preventing cognitive impairment in older people.

Ischemic post-conditioning is neuroprotective even at delayed tPA administration after embolic stroke in female rats.

Objectives: Delayed tissue plasminogen activator (tPA) thrombolysis is accompanied by different complications in stroke patients. Studies reported sex differences in stroke therapy. Ischemic postconditioning (PC) unveils neuroprotection in stroke models. In this study, we investigate the combined effect of delayed tPA therapy and PC procedure during an embolic stroke experimental model in female rats. Materials and Methods: Female Wistar rats were randomly divided into control (saline), tPA, PC, and tPA+PC groups after stroke induction via clot injection to the middle cerebral artery. tPA treatment was initiated 6 hr after stroke, and PC procedure was performed 6.5 hr post-ischemia induction (occlusion: 10 sec; reopening: 30 sec; 5 cycles). The cerebral blood flow (CBF) was recorded up to 60 min from IV tPA injection time. The parameters of brain edema, infarct volume, disruption of the blood-brain barrier (BBB), behavioral tests, and matrix metalloproteinases-9 (MMP-9) were evaluated. Results: This study revealed that PC conduction prevents excessive CBF increase by tPA and played a protective role in infarct volume reduction (P<0.05). The combination of PC and tPA reduced the infarct volume, brain edema, and protected BBB. tPA+PC could alleviate neurobehavioral disorders compared with control or tPA. Moreover, PC had the capability of MMP-9 reduction when combined with delayed tPA (P<0.05). Conclusion: Conduction of PC not only alleviated some stroke complications but also enhanced the therapeutic time window of tPA in female rats under embolic stroke.

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. Highlights: Memantine modulated excitatory receptive fields in the rat somatosensory cortex.Memantine decreased integrative receptive fields in rat somatosensory cortex. Plain Language Summary: As an NMDA receptor antagonist, memantine is used to treat moderate to severe Alzheimer's disease. Memantine has beneficial effects on cognition, mood, and perform daily activities. However, the current study results suggested that memantine may affect information processing in the somatosensory system. This should be considered for future research in the clinic.

Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice.

Cisplatin is one of the synthetic cancer medicines with nephrotoxicity being one of its major side effects. Past research shows that calcium dobesilate (CaD), as a vascular protective agent in diabetic retinopathy, has antioxidant properties. Thus, this study aims to evaluate the protective effects of CaD in cisplatin-induced nephrotoxicity in mice. A many as 28 mice, in the present experimental research, were randomly distributed into four groups, including control, cisplatin (the intraperitoneal administration of 20 mg/kg cisplatin only on the first day of the experiment), cisplatin + CaD 50 (cisplatin with the oral administration of 50 mg/kg CaD), and cisplatin + CaD 100 (cisplatin with the oral administration of 100 mg/kg CaD). The treated groups received CaD by oral gavage for 4 constitutive days. On the fifth day, the mice were sacrificed, and some biochemical (serum levels of Cr and BUN, renal tissue levels of MDA, and renal activities of SOD and GPx) and pathological parameters were evaluated. Based on the results, there was a significant decrease in the renal SOD and GPx activities; in contrast, there was a significant increase in the BUN, Cr, and renal MDA levels following administering cisplatin. However, the CaD treatment (100 mg/kg) significantly attenuated these alterations. In addition, the kidney's histological examination of kidneys confirmed the nephroprotective effects of CaD. The findings proved the protective impact of CaD on cisplatin-induced nephrotoxicity by an improvement in the oxidative stress factors.

Investigation of grape sap on wingless/integrated and ß-catenin genes expression with histological factors on the hair follicle in rat.

BACKGROUND AND PURPOSE: Natural products are used to improve the damage caused by harmful reagents in various pathological situations. This study investigated the effect of grape sap as a natural product with antioxidant properties on follicle cell proliferation in bleomycin (as a chemotherapy agent with toxic effects on hair growth) treated rats skin. EXPERIMENTAL APPROACH: The bleomycin treated rats were administrated grape sap. Wingless/integrated (wnt) and ß-catenin gene expression as follicle proliferative markers were evaluated using real-time polymerase chain reaction. Furthermore, histological factors and total antioxidant capacity were evaluated. FINDINGS / RESULTS: The data showed that, grape sap increased the number of anagenic hair follicle in grape sap (100 mg/kg) group (P < 0.001), sebaceous glands (P < 0.001), blood vessel density (P < 0.001), and hair growth length (P < 0.001). Also, wnt and ß-catenin gene expression was elevated. The data showed that wnt and ß-catenin gene expression were elevated in grape sap treated animals versus bleomycin group (P < 0.01 and 0.001, respectively). CONCLUSION AND IMPLICATIONS: Our finding showed that grape sap can be effective in increasing hair growth a gains bleomycin toxic effects on skin hair growth.

The therapeutic approaches of renal recovery after relief of the unilateral ureteral obstruction: A comprehensive review.

Unilateral ureteral obstruction (UUO) as a clinical disorder can cause renal damage. The permanent injury occurs if the obstruction is not relieved. Renal injury can be reversed with UUO removal (RUUO). RUUO attenuates the renal hemodynamic and functional impairment and decreases the renal fibrosis and apoptosis. Nevertheless, kidney injury may continue after RUUO, and synchronous medication therapy seems necessary. However, UUO and post-RUUO periods are also important in final renal recovery. To date, various therapeutic strategies have been applied to develop renal recoverability after RUUO. In animal studies, the effect of some pharmacological agents such as mesenchymal stem cells, anti-inflammation drugs, L-arginine, bone morphogenetic protein-7, epidermal growth factor, allopurinol, renin-angiotensin system antagonists, and endothelin A/B receptor blocker were surveyed in RUUO model. Also, post-RUUO renal recoverability has been studied in human researches. In these studies, the effective strategies have focused on surgery for RUUO creation via urethrotomy, urethroplasty, stent balloon dilatation, and stenting. Accordingly, in this review, we focused on the therapeutic procedure of renal recovery after the RUUO situation in human and animal studies.