Pharmaceutical and Biomedical Research

Could Celastrol Be a Photosensitizer for Photodynamic Therapy to Combat SARS-CoV-2?

Siukan Law — 2022-10-30

The Article Abstract is not available.

A Narrative Review of SARS-CoV-2 Pathogenesis, Transmission, and Clinical Manifestations

Amin Sharifan — 2022-10-30

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has become a major global concern. As of writing this manuscript, there are over 224 million cases diagnosed, and 4.5 million recorded deaths with the Coronavirus Disease 2019 (COVID-19).

Objectives: This article reviews the studies conducted on SARS-CoV-2 pathogenesis, transmission, and different clinical manifestations.

Methods: An extensive online search was conducted on PubMed and Google Scholar search engines. The following keywords and their combinations were used to complete this review: “SARS-CoV-2”, “COVID-19”, “virology”, “mechanism of action”, “transmission”, “clinical manifestations”, “laboratory findings”, and “comorbidities.”

Results: The SARS-CoV-2 spike glycoprotein recognizes the human angiotensin-converting enzyme 2 receptors, and through that, the virus can enter its host cell. The virus is mainly transmitted via respiratory and or airborne droplets. The severity of the COVID-19 clinical manifestations relies on the associated comorbidities and or old age, which ranges from littleto-no symptoms to severe and critical conditions. Fever, loss of appetite and or smell, fatigue, and dry cough are among the most reported symptoms. Underlying conditions may lead to severe or critical stages of COVID-19.

Conclusion: The SARS-CoV-2 nucleocapsid and receptor-binding domain could be two potential targets for future vaccines and drugs. It appears that the virus is adapting to each region’s specific environment; therefore, new endemic variants are forming.

Protective Effects of N-Acetylcysteine on Dipentyl Phthalate Induced Cognitive Dysfunction and Brain Oxidative Stress in Mice

Sandhya Rani Gautam — 2022-10-30

Background: Dipentyl phthalate (DPeP) is a plasticizer compound commonly used in polyvinylchloride plastic to enhance softness and flexibility. They are not bound covalently to plastic polymers; therefore, they can dissolve into the environment and adversely affect the health of humans and animals.

Objectives: The aim of this study was to investigate the effect of DPeP on cognition and protective effects of N-acetylcysteine (NAC) on DPeP induced alteration in cognitive behaviour and oxidative stress markers in mice.

Methods: Mice were orally treated with 2 doses (33 mg/kg and 100 mg/kg) of DPeP for 28 days. Cognitive functions were assessed using spatial navigation tasks on the Morris water maze and the step-down latency in the passive avoidance apparatus. Oxidative stress was assessed by examining the levels of malondialdehyde, glutathione, ferric reducing antioxidant power, and 8-hydroxy-deoxyguanosine levels in the whole brain of mice.

Results: There was a significant increase in latency in spatial navigation tasks and a significant decline in the step-down latency in passive avoidance apparatus in the DPeP-treated group compared to the control groups. There was also a significant increase in the levels of oxidative stress following DPeP administration as seen with the rise in the levels of malondialdehyde, 8-hydroxy-deoxyguanosine, and a fall in glutathione and ferric reducing antioxidant power levels.

Conclusion: The present study demonstrated that DPeP adversely affects learning and memory functions in mice by oxidative stress-mediated neuronal damage. These effects were attenuated by pretreatment with N-acetylcysteine.

Comparing the Effects of Consuming Propolis and Chicory for Eight Weeks and Resistance Training on Histopathological and Morphometric Changes of Uterine Tissue in Rats Treated With Testosterone Enanthate

Sodabeh Movahed — 2022-10-30

Background: The illegal use of anabolic and androgenic steroids is a public health problem and their side effects in women are different from the side effects observed in men.

Objectives: This study aims to compare the effects of consuming propolis and chicory for 8 weeks and resistance training on histopathological and morphometric changes of the uterine tissue in rats treated with testosterone enanthate.

Methods: In this experimental study, 40 female Wistar rats were randomly divided into 5 groups (n=8): control (placebo), sham (resistance training), resistance training plus testosterone enanthate (20 mg/kg body weight), resistance training plus testosterone enanthate+chicory (6 g/kg body weight), and resistance training plus testosterone enanthate plus propolis (400 mg/kg body weight). The resistance training protocol was performed 5 sessions per week in 4 rounds with an intensity of 40% to 160% of the body weight of the mice for 8 weeks. After weighing and dissection, the uterine tissue was examined histologically.

Results: The thickness of the endometrial layer in the sham, testosterone, and propolis groups showed a significant decrease compared to the control group (P<0.05). There was a significant decrease in the thickness of the functional layer in the sham, testosterone, chicory, and propolis groups compared to the control group (P<0.05). The thickness of the basal layer showed a significant decrease in the testosterone and propolis groups compared to the control group (P<0.05). Glands in the testosterone, chicory, and propolis groups showed a significant decrease compared to the control group (P<0.05). The thickness of the myometrial layer showed a significant decrease in the testosterone group compared to the control, sham, chicory, and propolis groups (P<0.05).

Conclusion: The results showed that high-intensity resistance training combined with the use of testosterone enanthate causes histopathological changes in the uterus of female rats. Meanwhile, the use of propolis and chicory can improve the effects of testosterone enanthate as a treatment option.

Molecular Characterization of a cDNA Encoding of an Anionic Cysteine-Free Antimicrobial Peptide From the Iranian Scorpion Odontobuthus Doriae Venom Glands

Amir Jalali — 2022-10-30

Background: The venom peptides from the scorpion fauna of Iran have been poorly characterized so far.

Objectives: In this study, we identified a cDNA encoding of an anionic cysteine-free antimicrobial peptide from the Iranian yellow scorpion odontobuthus doriae (O.doriae).

Methods: The cDNA sequence of an anionic antimicrobial-peptide (AMP) was determined from the venom gland cDNA library of Iranian yellow scorpion O.doriae and was named ODAMP5. This sequence was characterized by a software. Then, the structure and function of its putative peptide were predicted in a bioinformatics manner. The library was constructed from 6 scorpion venom glands. The cDNA related to ODAMP5 was isolated from one positive clone of the library.

Results: The analysis of ODAMP5 reveals a 51-residue mature peptide with an anionic property that was stable in physiological states. ODAMP5 was similar to anionic peptide Aba-2 from Androctonus bicolor and according to its structure, it can be a member of helical structure AMPs with a new type of putative conserved domain. Putative ODAMP5 has a small size which makes it convenient for synthesis.

Conclusion: Furthermore, we created a framework to express the ODAMP5 peptide for future biomedical and pharmacological studies. ODAMP5 may be a new suitable therapeutic strategy for bacterial infection among a few recognized scorpion venom peptides without disulfide bridges.

Volatile Constituents and Toxicity of Essential Oils Extracted From Aerial Parts of Plantago Lanceolata and Plantago Major Growing in Iran

Samaneh Rahamouz Haghighi — 2022-10-30

Background:Plantago lanceolata L. (P. lanceolate) and Plantago major L. (P. major) belong to the Plantaginaceae family and are widely used in traditional medicine.

Objectives: This study aims to qualitatively identify the crucial compounds and evaluate the toxicity effects of essential oils of two Plantago species.

Methods: The plantains were collected from Zanjan Province, Iran. The essential oils were extracted by hydrodistillation and then analyzed using gas chromatography coupled with mass spectrometry (GC/MS). The toxicity effects of the essential oils were evaluated on HCT-116 and HEK-293 cell lines (in vitro MTT assay) and Artemia salina (A.salina) (in vivo assay). The constituents of the essential oils were identified by calculating their retention indices under temperature-programmed conditions for n-alkanes (C8 -C20) in the Agilent 19091S-433 column.

Results: The main identified constituents were metaraminol (14.04%), bifemelane (8.73%), metossamina (8.16%), and pterin-6-carboxylic acid (5.11%) in P. lanceolata and 2-dodecen-1-yl (-) succinic anhydride (15.29%), benzenemethanol, α-(1-aminoethyl)-2,5- dimethoxy-(11.83%), dl-phenylephrine (7.51%), and nortriptyline (5.15%) in P. major. The essential oils of P. major exhibited more antiproliferative properties on HCT-116 at 72 h compared to P. lanceolata (IC50: 102.66 µg/mL). At 400 µg/mL of P. lanceolata and P. major, the percentage of the lethality of nauplii was 8% and 12%, respectively (LC50:2242.57 µg/ mL and 1783.7 µg/mL). The present study showed that the most of constituents of oils were alcohols and amines.

Conclusion: Some of the compounds identified in the Plantago species essential oils have important pharmaceutical properties. This study reported the cytotoxicity of essential oils on the colon cancer cell line. However, the essential oils were not toxic against A.salina at the examined concentrations.

Effects of Hydroalcoholic Extract of Lepidium Sativum L. on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Mohammad Shokrzadeh — 2022-10-30

Background: Carbon tetrachloride (CCl4 ) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis. Lepidium sativum contains flavonoids, alkaloids, and antioxidant components.

Objectives: This study aims to investigate the hepatic protection of L. Sativum Extract (LSE) on CCl4 -induced hepatotoxicity in mice.

Methods: A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4 , and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis.

Results: Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P<0.05), AST in all doses (P<0.001), and ALP in 600 mg/kg (P<0.001). In addition, LSE treatment significantly increased GSH in 400 mg/kg (P<0.01) and 600 mg/kg (P<0.001).

Conclusion: LSE has hepatic protective activity against CCl4 -induced injuries. The possible anti-hepatotoxic mechanisms may be related to the presence of flavonoids, triterpenes, alkaloids, tannin, and coumarins in the LSE by inhibiting the free radicals mediated damage.

Successful Diflunisal Desensitization in a Transthyretin Amyloidosis Patient With Ibuprofen Allergy: A Case Report

Jialing Aw — 2022-10-30

Background: Amyloid diseases are hereditary and include transthyretin (TTR) amyloidosis where subunit protein mutations may occur in genes for TTR, leading to the deposition of fibrils (low molecular weight subunits (5 to 25 KD of proteins) in extracellular tissues. By reducing the formation of TTR amyloid, diflunisal, a nonsteroidal anti-inflammatory drug, can preserve the quality of life and significantly reduce disease progression. We present a case of a 61-year-old male patient with a history of ibuprofen allergy, diagnosed with TTR amyloidosis, complicated with peripheral neuropathy, cardiac, and liver amyloid. He developed bilateral mild eye swelling from the ibuprofen oral provocation test. With a similar structural backbone of carboxylic acid, he could develop pseudoallergy to diflunisal with an unknown likelihood of developing an allergic reaction.

Objectives: This study aims to design successful diflunisal desensitization in a patient with TTR amyloidosis.

Methods: The patient underwent a 14-step diflunisal desensitization procedure using 2 tablets of diflunisal 500 mg that was dissolved in 40 mL of sodium bicarbonate 8.4% injection to create serial 10-fold dilutions. Oral desensitization was administered in the escalation of the doses at 30-min intervals, with a starting dose of 0.1 mg until a final dose of 250 mg was reached.

Results: The patient tolerated diflunisal desensitization and was continued on diflunisal treatment without any evidence of an allergic reaction.

Conclusion: Diflunisal desensitization can be considered in patients with a history of ibuprofen allergy if there are no available alternative treatments. To the best of our knowledge, this is the first article describing a patient with angioedema to ibuprofen who could tolerate oral diflunisal after desensitization.