Publications by authors named "Mohammad Mehdipour"

5 Publications

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Contribution of Lysosome and Sigma Receptors to Neuroprotective Effects of Memantine Against Beta-Amyloid in the SH-SY5Y Cells.

Adv Pharm Bull 2020 Jul 11;10(3):452-457. Epub 2020 May 11.

Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.

Memantine is an approved drug for the treatment of Alzheimer's disease (AD). Autophagy, lysosome dysfunction, and sigma receptors have possible roles in the pathophysiology of AD. Therefore, we aimed to investigate the contribution of sigma receptors and lysosome inhibition to the neuroprotective effects of memantine against amyloid-beta (Aβ)-induced neurotoxicity in SH-SY5Y cells. We determined the neuroprotective effects of memantine (2.5 µM), dizocilpine (MK801, as a selective N-methyl-D-aspartate (NMDA) receptor antagonist) (5 μM) against Aβ25- 35 (2 μg/μL)-induced neurotoxicity. We used chloroquine (10, 20, and 40 μM) as a lysosome inhibitor and BD-1063 (1, 10, and 30 μM) as a selective sigma receptor antagonist. The MTT assay was used to measure the neurotoxicity in the SH-SY5Y cells. Data were analyzed using the one-way ANOVA. Memantine (2.5 µM), dizocilpine (5 µM), chloroquine (10 and 20 µM) and BD-1063 (1, 10 and 30 µM) decreased the neurotoxic effects of Aβ on the SH-SY5Y cells. However, chloroquine (40 µM) increased the neurotoxic effects of Aβ. Cell viability in the cells treated with memantine + Aβ + chloroquine (10, 20, and 40 μM) was significantly lower than the memantine + Aβ-treated group. Moreover, cell viability in the memantine + Aβ group was higher than the memantine + Aβ + BD-1063 (10 and 30 μM) groups. The lysosomal and sigma receptors may contribute to the neuroprotective mechanism of memantine and other NMDA receptor antagonists. Moreover, the restoration of lysosomes function and the modulation of sigma receptors are potential targets in the treatment of AD.
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http://dx.doi.org/10.34172/apb.2020.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335986PMC
July 2020

Protective effect of standardized extract of Myrtus communis L. (myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study.

Drug Chem Toxicol 2018 Oct 11;41(4):408-414. Epub 2018 May 11.

e Department of Agriculture , Azad University of Kerman , Kerman , Iran.

Context: Myrtle (Myrtus communis L) has been used widely in traditional medicine for different respiratory disorders. Idiopathic pulmonary fibrosis (IPF) is an inflammatory disease characterized by progressive loss of lung function with poor prognosis. The pathogenesis of disease has not been completely elucidated, but probably persistent epithelial damages are involved.

Objective: Evaluation of biochemical and histopathological effect of preventive and therapeutic doses of myrtle against bleomycin (BLM)-induced pulmonary fibrosis (PF) in animal model.

Materials And Methods: Methanolic extract of M. communis was prepared by maceration method. Total flavonoid content was determined and experimentally PF was induced in rat with intratracheal instillation of a single dose of BLM (5 mg/kg) only on day 0. Myrtle antifibrotic effect was evaluated as preventive (50 mg/kg/day, intraperitoneal (i.p.) injection, from day 0-13) and therapeutic agent (50 mg/kg, i.p., from day 14-27) in comparison with methyl prednisolone (M-pred) (4 mg/kg, i.p. for 14 days).

Results: Parenchymal inflammation and fibrotic changes significantly were reduced by myrtle and M-pred. Significant decrease in hydroxyproline content and lipid peroxidation were observed in animals receiving myrtle extract while catalase activity was increased by myrtle. Improvement in inflammation and fibrosis was observed in myrtle group especially in the early phase of fibrosis (preventive regime).

Discussion And Conclusion: Myrtle extract effectively inhibited the inflammation and fibrosis of lung parenchyma in both preventive and therapeutic methods. This effect might be due to the reduction of tissue inflammation and inhibition of oxidative stress. More studies are being carried out to find main mechanisms and separation of active compounds.
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http://dx.doi.org/10.1080/01480545.2018.1459670DOI Listing
October 2018

Anti-Inflammatory Subfractions Separated from Acidified Chloroform Fraction of Fenugreek Seeds (Trigonella foenum-graecum L.).

J Diet Suppl 2018 Jan 30;15(1):98-107. Epub 2017 May 30.

b Neuroscience Research Center, Faculty of Pharmacy , Kerman University of Medical Sciences , Kerman , Iran.

Considering the side effects of current anti-inflammatory drugs, novel therapeutic agents are desired. We have succeeded in separating flavonoid-rich fractions with anti-inflammatory effect from fenugreek seeds (Trigonella foenum-graecum L.). In this work, we aimed to carry out further fractionation to find active anti-inflammatory subfractions. Trigonelline content of the plant was determined by spectrophotometric method. Fenugreek seeds were extracted consecutively with petroleum ether, acidified chloroform (ACC), alkaline chloroform (AKC), methanol, and water. ACC fraction, which had exhibited the highest anti-inflammatory effect, was further fractionated using column chromatography. Obtained subfractions were evaluated using carrageenan-induced paw edema (CIPE) method. Animals were pretreated by test compounds, and after 30 minutes edema was induced by subcutaneous injection of 100 µl of 1% w/v carrageenan into the right paw of animals. Volume difference of both paws was measured at different times after carrageenan injection. The concentration of trigonelline was determined as 16.2%. ACC fraction inhibited paw edema significantly in comparison to control (p < .05). Four subfractions (dry weight percentage basis) were selected for pharmacological study. F3 subfraction exhibited the greatest inhibition at 15 mg/kg (p < .001). ACC fraction and F4 significantly inhibited paw edema at doses of 5, 10, and 15 mg/kg (p < .001). Phytochemical studies indicated the presence of flavonoids in ACC and active subfractions. Further separation can lead to finding active components from active subfractions, which probably belong to flavonoid phytochemicals. Considering the gastroprotective effect of fenugreek, we hope the separated fractions also would be free of gastrointestinal side effects.
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http://dx.doi.org/10.1080/19390211.2017.1326431DOI Listing
January 2018

Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.

Iran Red Crescent Med J 2016 Nov 17;18(11):e26613. Epub 2016 Aug 17.

Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, IR Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, IR Iran.

Background: A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans.

Objectives: This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame ( L.), wild pistachio ( Desf.), hemp ( L.), and walnut ( L.).

Methods: Twenty-four mice were selected based on simple random sampling. Twenty-five percent of the total body surface area was burned by exposure to boiling water, according to the Walker-Mason method. NF and silver sulfadiazine (the positive control) were applied topically twice a day for 21 days. The burned area in the negative control group was left untreated. Epithelialization time and the percent of wound contraction were measured during the treatment period. The process of wound repairing was evaluated using histological (H and E and trichrome staining) and immunohistological (anti-pancytokeratin) methods.

Results: When compared to the controls, NF significantly improved wound contraction after day 10. Epithelialization time in the NF group was significantly faster than in the other groups (20 vs. 25.5 days) (P < 0.001). Histopathological and immunohistochemical findings confirmed the efficacy of the NF.

Conclusions: A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.
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http://dx.doi.org/10.5812/ircmj.26613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292211PMC
November 2016

Investigation of association between donors' and recipients' NADPH oxidase p22(phox) C242T polymorphism and acute rejection, delayed graft function and blood pressure in renal allograft recipients.

Transpl Immunol 2015 Jan 28;32(1):46-50. Epub 2014 Aug 28.

Physiology Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran; Department of Nephrology, Urology and Renal Transplantation, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Background: Production of reactive oxygen species (ROS) and thereby induction of oxidative stress seem to be one of the major mediators of inflammatory adverse outcomes after renal transplantation. p22(phox) is a polymorphic subunit of NAD(P)H-oxidase that is critical for activation and stabilization of the enzyme. This enzyme is involved in the production of superoxide that triggers inflammatory injuries to the kidney. So in this study, the association between donors and recipients' C242T polymorphism of p22(phox) and acute rejection (AR), delayed graft function (DGF), creatinine clearance (CrCl), and blood pressure in renal-allograft recipients was studied.

Methods: One hundred ninety six donor-recipient pairs were studied. The C242T polymorphism of p22(phox) was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to p22 genotype, the subjects were divided in wild-type (CC) and T allele carriers (CT+TT). Transplantation outcomes were determined using acute rejection and delayed graft function criteria. The mean arterial pressure was also measured monthly after transplantation.

Results: There was a significant association between the recipients' p22(phox) polymorphism and DGF occurrence (OR=2.5, CI: 1.2-4.9, p=0.0009). No significant association was detected between donors' p22(phox) polymorphism and AR and DGF events. CrCl during the six months follow-up after transplantation was lower in the patients who received allograft from donors carrying 242T allele (B=-12.8, CI: -22.9-12.8 (-22.9 to -2.6)). Changes in the blood pressure were not different among the patients having different genotypes of p22(phox).

Conclusion: These results suggest that the recipients' p22(phox) C242T polymorphism may be a major risk factor for DGF in renal transplantation. Moreover, the donors' 242T allele seems to affect the rate of CrCl in the renal allograft recipients.
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http://dx.doi.org/10.1016/j.trim.2014.08.004DOI Listing
January 2015