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ABSTRACT Acetaminophen (APAP) is a well‐known drug that, in high doses, induces hepatotoxicity and nephrotoxicity. This study has investigated the preventive effect of the extract and fractions of Ribes khorasanicum on APAP‐induced liver and kidney damage. In this experiment, after analysis of the extract using FTIR, toxicity was induced by APAP on the 7th day. Before that, the extract and their aqueous, ethyl acetate, and n‐hexane fractions were administrated orally. 24 h after APAP administration, the animals were sacrificed. The liver and kidney were removed for the evaluation of oxidation and biochemical markers, including SGOT, SGPT, ALP, LDH, albumin, urea, creatinine, and bilirubin and also for histopathological evaluations. The safety of the extract was evaluated based on the MTT. Also, expression of the NF‐kB is done. Administration of Ribes khorasanicum significantly decreased the biochemical parameters compared to the APAP. Oxidative parameters, as well as histopathological changes in preventive groups, were improved compared to the APAP in both tissues. The results showed that the aqueous and ethyl acetate fractions of the extract had a better effect than the whole extract and n‐hexane fraction against APAP toxicity. [ABSTRACT FROM AUTHOR]

The midbrain dorsomedial periaqueductal grey column (dmPAG) is involved in the regulation of cardiovascular responses. Due to the presence of Gamma‐Aminobutyric acid (GABA) receptors in the dmPAG, this study aimed to investigate the role of GABAA receptors in the dmPAG on cardiovascular parameters and its possible peripheral mechanisms. The left femoral artery was cannulated, and systolic arterial pressure (SAP), mean arterial pressure (MAP) and heart rate (HR) were recorded using a Power lab system. Microinjection of saline, muscimol and bicuculline (BIC) was done using a stereotaxic device. Also, the peripheral mechanisms dependent on GABAA receptors in the dmPAG were evaluated by intravenous (i.v.) injection of hexamethonium (Hexa) and atropine (Atr) 5 min before the BIC. Results showed that BIC significantly increased ∆SAP, ∆MAP and ∆HR than the control group, but muscimol had no significant effect. Injection of Hex significantly attenuates the effect of BIC on ∆SAP and ∆MAP. Atr (i.v) significantly increased the ∆HR, and when injected before BIC microinjection, it did not affect the cardiovascular responses induced by BIC. These findings show that GABAA receptors of the dmPAG have inhibitory effects on the cardiovascular system, which are mostly mediated by the sympathetic system. [ABSTRACT FROM AUTHOR]

Objective(s): Due to the presence of the cholinergic system in the lateral periaqueductal gray (lPAG) column, the cardiovascular effects of acetylcholine (ACH) and its receptors in normotensive and hydralazine (HYD) hypotensive rats in this area were evaluated. Materials and Methods: After anesthesia, the femoral artery was cannulated and systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and also electrocardiogram for evaluation of low frequency (LF) and high frequency (HF) bands, important components of heart rate variability (HRV), were recorded. ACH, atropine (Atr, a muscarinic antagonist), and hexamethonium (Hex, an antagonist nicotinic) alone and together microinjected into lPAG, changes (Δ) of cardiovascular responses and normalized (n) LF, HF, and LF/HF ratio were analyzed. Results: In normotensive rats, ACH decreased SBP and MAP, and enhanced HR while Atr and Hex did had no effects. In co-injection of Atr and Hex with ACH, only ACH+Atr significantly attenuated parameters. In HYD hypotension, ACH had no affect but Atr and Hex significantly improved the hypotensive effect. Co-injection of Atr and Hex with ACH decreased the hypotensive effect but the effect of Atr+ACH was higher. In normotensive rats, ACH decreased nLF, nHF, and nLF/nHF ratio. These parameters in the Atr +ACH group were significantly higher than in ACH group. In HYD hypotension nLF and nLF/nHF ratio increased which was attenuated by ACH. Also, Atr+ACH decreased nLF and nLF/nHF ratio and increased nHF. Conclusion: The cholinergic system of lPAG mainly via muscarinic receptors has an inhibitory effect on the cardiovascular system. Based on HRV assessment, peripheral cardiovascular effects are mostly mediated by the parasympathetic system. [ABSTRACT FROM AUTHOR]

Objective(s): In the present study, the cardiovascular effects of glutamate NMDA receptor of the pedunculopontine tegmental nucleus (PPT) in normotensive and hydralazine (HLZ) hypotensive rats were evaluated. Materials and Methods: In the normotensive condition, MK-801(1 nmol; an NMDA receptor antagonist) and L-glutamate (L-Glu, 50 nmol an agonist) alone and together were microinjected into the nucleus using a stereotaxic device. In hypotensive condition, 2 min after induction of hypotension by HLZ (10 mg/kg, intravenous), drugs, same as in normotensive condition, were microinjected into the PPT. Recorded mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were recorded throughout the experiment by a Power lab apparatus that was connected to a catheter inserted into the femoral arty. The cardiovascular changes (Î") induced by microinjection drugs were computed and statistically analyzed. Results: In the normotensive condition, L-Glu significantly increased ΔMAP and ΔSBP (P<0.001) and decreased ΔHR (P<0.01) compared with the control. MK-801 alone significantly increased HR (P<0.05) while co-injected with L-Glu + MK-801 it significantly attenuated the L-Glu effect on ΔMAP and ΔSBP but augmented ΔHR (P<0.01). In the hydralazine hypotension condition, L-Glu significantly improved hypotension (P<0.01) and deteriorated bradycardia induced by HLZ (P<0.05). MK-801 alone did not significantly affect ΔMAP, ΔSBP, and ΔHR but when co-injected with L-Glu (L-Glu + MK-801) it could significantly attenuate the cardiovascular effect of L-Glu in the PPT. Conclusion: We found that activation of NMDA receptors of the glutamatergic system in the PPT evoked blood pressure and inhibited HR in both normotensive and hypotensive conditions in rats. [ABSTRACT FROM AUTHOR]

Introduction: The central mechanism related to the cardiovascular response to lipopolysaccharide (LPS)-induced hypotension is not entirely known, but it is suggested that numerous brain areas such as dorsal periaqueductal gray (dPAG) are involved in this process. In the current work, the cardiovascular effect of the dPAG during LPS-induced hypotension is investigated. Methods: The study animals (rats) were divided into four groups: control (saline microinjected into dPAG), lidocaine 2%, LPS (intravenously injected), and lidocaine + LPS. Catheterization of the femoral artery and vein was performed to record blood pressure and LPS injection, respectively. Saline and lidocaine were microinjected into the dPAG nucleus then the LPS injection was performed. The changes (Δ) in systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were measured and compared with those of the control and LPS groups. Results: LPS significantly declined ΔMAP and ΔSBP (P<0.05) but did not change the ΔHR compared to the control. Lidocaine did not significantly affect basic ΔSBP, ΔMAP, and ΔHR compared to the control. Injection of lidocaine before LPS significantly attenuated the reduction of ΔSBP and ΔMAP evoked by LPS (P<0.05). Conclusion: Our data showed that blockade of the dPAG by lidocaine significantly ameliorates the hypotension induced by LPS. this finding confirms the involvement of the dPAG in cardiovascular regulation during LPS-induced hypotension. [ABSTRACT FROM AUTHOR]

The Olibanum the resin of Boswellia serrata is assumed that attenuates the generation of pro-inflammatory and oxidant agents, reinforces the anti-inflammatory cytokines and anti-oxidant agents to improve memory impairment induced by lipopolysaccharide (LPS). The rats were treated as: (1) saline, (2) LPS, (3 and 4) Olibanum 100 or 200 mg/kg plus LPS. In the Morris water maze (MWM), LPS increased the duration and the distance traveled to find the platform while decreased the time spent and the distance traveled in the target quadrant. Moreover, LPS decreased the step-through latency to enter the dark in passive avoidance (PA). Pretreatment with Olibanum enhanced the performances of the rats in MWM and PA tests. LPS also increased IL-6, TNF-α, NO, GFAP, and MDA levels while decreased IL-10, BDNF, CAT, SOD, and thiol. Olibanum reversed the effects of LPS. Olibanum showed anti-inflammatory and antioxidant properties. It could improve memory impairment induced by LPS. [ABSTRACT FROM AUTHOR]

Objective(s): Periaqueductal gray (PAG) is a mesencephalic area divided into four columns including ventrolateral periaqueductal gray (vlPAG). vlPAG plays a role in cardiovascular regulation during normal and hemorrhagic (Hem) conditions. Due to presence of glutamate in this area, we evaluated the effect of glutamatergic receptors of this area on cardiovascular activity in normotensive and hypovolemic Hem rats. Materials and Methods: Animals were divided into twelve groups: saline (vehicle), Glutamate, GYK52466 (non-NMDA receptor antagonist), and MK801 (NMDA receptor antagonist) with and without Glu microinjected into vlPAG in normal and Hem conditions. Following the femoral artery cannulating and microinjecting, changes (Δ) of heart rate (HR), systolic blood pressure (SBP), and mean arterial pressure (MAP) were recorded via a PowerLab unit. Results: In normotensive conditions, microinjection of Glu increased ΔMAP, ΔSBP, and ΔHR (P<0.001). MK-801 and GYKI-52466 nonsignificant reduced cardiovascular responses than vehicle while their changes were significant compared with glutamate (P<0.001). Co-injection of GYKI- 52466 with Glu did not significantly reduce ΔSBP and ΔMAP induced by Glu (P>0.05) but co-injection of MK-801 with Glu significantly attenuate these effects(P<0.01). In Hem, Glu increased ΔSBP, ΔMAP, and ΔHR (P<0.05). GYKI-52466 alone did not change cardiovascular responses but MK-801 decreased ΔSBP than Hem (P<0.01). Co-injection of GYKI-52466 with Glu had significant(P<0.05) but MK-801 with Glu had no significant effect compared with Hem (P>0.05). Conclusion: The glutamatergic system of vlPAG increases cardiovascular values that are mostly mediated through the NMDA receptor. Since vlPAG is well known as an inhibitory region, it seems that glutamate does not have a noteworthy cardiovascular role in vlPAG during Hem and normal conditions. [ABSTRACT FROM AUTHOR]

The saffron petalsare a by-product part of the saffron flower with a cardiovascular effect. This study evaluated the effect of the saffron petalon hypertension induced by angiotensin II (AII) and NG-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). Rats were divided into 11 groups: 1) Control, 2) AII (50.00 ng kg-1), 3) Losartan+ AII, 4) L-NAME (10.00 mg kg-1), 5) sodium nitroprusside (SNP) + L-NAME, 6, 7) Saffron petals extract; 8, 9) saffron petals (100 and 200 mg kg-1) + AII and 10,11) saffron petals (100 and 200 mg kg-1) + L-NAME. Hypertension induced by intravenous injection of AII and L-NAME in separate groups. In treated groups, 30 min before injection of AII or L-NAME rats received two doses of extract via intraperitoneal administration. The femoral artery was cannulated and cardiovascular parameters recorded by a transducer connected to power lab apparatus. Maximal changes (∆) of mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (HR) from baseline were calculated and compared to with those in hypertensive and control groups. Results showed that both AII and L-NAME significantly increased SBP and MAP than control, however, HR in AII was decreased and in the L-NAME group increased. Pre-treatment with saffron petals could significantly attenuate the cardiovascular responses induced by both AII and L-NAME. However, the effect of the extract in AII hypertensive rats was more effective than L-NAME groups. The findings showed that the hydroalcoholic extract of the saffron petals had an antihypertensive effect that mainly was mediated by inhibition of AII activity. [ABSTRACT FROM AUTHOR]

Due to the antioxidant effects of the Ziziphus jujuba Mill (Z. jujuba), we investigated the liver, heart, and brain-protective effects of this herb against toxicity induced by adriamycin (ADR). In this study, Wistar rats were divided into 1) control, 2) ADR and 3, 4, and 5) treated groups orally administrated three doses of Z. jujuba hydroalcoholic extract for 1 month. The liver, heart, and brain were removed for evaluation of the oxidative markers. Blood samples were evaluated to determine the levels of Lactate dehydrogenase, total and direct bilirubin, alkaline phosphatase, Aspartate transaminase, and Alanine aminotransferase. Administration of Z. jujuba significantly decreased the biochemical enzymes compared to the ADR. Oxidative condition in treated rats with different doses of Z. jujuba was improved compared to the ADR group. Z. jujuba could decrease the oxidative injury through invigoration of the tissues antioxidant system. The mentioned hepatic and cardiac parameters levels improved during extract administration. Practical applications: In the first stage, our findings and other supplementary works have shown that administration of jujube extract has prevented the effects of histotoxicity caused by adriamycin, so it seems that in the next stage, the effects of this herbal plant on patients with tissue toxicity caused by adriamycin should be evaluated and if the results are positive in pharmacological studies, it should be used as a complementary drug in the treatment of these patients. [ABSTRACT FROM AUTHOR]

Objective(s): The 5-hydroxytryptamine1A (5-HT1A) receptor is one of the serotonin receptors in the brain, which regulates cardiovascular responses, especially in hemorrhage. Presence of this receptor in the cuneiform nucleus (CnF) has been shown. The present study evaluates the cardiovascular effect of this receptor of the CnF in normal and hypotensive hemorrhagic rats. Materials and Methods: Agonist (8-OH-DPAT) and antagonist (WAY-100635) of 5-HT1A microinjected into the CnF in basal and hemorrhagic conditions and cardiovascular responses were evaluated. Hemorrhage induced by blood withdrawal from the femoral artery and 2 min after that drugs microinjected. Time course and peak changes (A) of the mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (AHR) were obtained and compared to the control and hemorrhage groups. Results: In basal condition, 8-OH-DPAT significantly decreased ASBP, AMAP and AHR compared to the control (P<0.05-P<0.01), while way-100635 did not have a significant effect. Hypotension and tachycardia induced by hemorrhage ameliorated by agonist (P<0.05-P<0.01), while antagonist deteriorated hypotension (P<0.05) but attenuated tachycardia (P<0.01). Conclusion: This study shows that 5-HT1A receptor of the CnF involves in regulation of the cardiovascular responses. However, this effect in basal and hemorrhage conditions is different. [ABSTRACT FROM AUTHOR]