Iranian Journal of Pharmaceutical Sciences

Cadmium is a toxic metal that can lead to liver failure in humans and animals. Astaxanthin (ASX) is one of the well-known xanthophyll carotenoids in food that has remarkable antioxidant properties. Hence, this study investigated the effect of ASX against cadmium-induced hepatic failure. Twenty-four mice were divided into four groups of six each and treated intraperitoneally as follows: group 1 (sham) received normal saline and olive oil; group 2 received 10 mg/kg/day of ASX; groups 3 and 4 were treated with cadmium (1 mg/kg/day) and ASX (10 mg/kg/day) + cadmium (1 mg/kg/day), respectively. After 14 consecutive days, mice were sacrificed and blood and liver samples were isolated for histopathological and biochemical experiments. Our findings showed a significant increase in serum alanine aminotransferase level, as a hepatic marker, following cadmium administration (p < 0.05). In this regard, cadmium led to hepatic leukocyte infiltration, dilated sinusoids, and increased hepatic metallothionein level (p < 0.01). Following the administration of ASX, a significant improvement was found in the metallothionein level and hepatic enzymes alongside histopathologic alterations. The present study revealed that the administration of ASX could prevent cadmium-induced hepatic failure, which may be related to the antioxidant properties of this carotenoid.

Neuropathic pain due to vincristine administration is an important dose limiting adverse effect with no definite efficient treatment. Citrus aurantium possesses multiple therapeutic potentials and is commonly used in traditional medicine. This study investigate the possible effects of the hydroethanolic extract of C. aurantium (CA) leaves and magnesium sulfate (MgSO4) as a known analgesic in vincristine-induced peripheral neuropathy (VIN). Vincristine was administered intraperitoneally (IP) to establish peripheral neuropathy in mice. Effects of CA (50,100 and 150 mg/kg, IP) and MgSO4 (50, 75 and 100 mg mg/kg, IP) were assessed on pain threshold performed by hot plate test. Moreover, the serum levels of total antioxidant capacity (TAC) and malondialdehyde (MDA) were assayed. Administration of CA (100 and 150 mg/kg) showed significant (p<0.001) decrease in responses to pain. In addition, MgSO4 in high dose of 100 mg/kg could alleviate the neuropathic symptoms. The result of biochemical tests exerted high TAC level in all CA treated groups (p<0.01 in 50 mg/kg and p<0.001 for 100 and 150 mg/kg). MDA level was decreased significantly (p<0.001) by CA (100 and 150 mg/kg) and MgSO4 (100 mg/kg). However the combination of low dose of CA and MgSO4 exerted no efficient antinociceptive effect. According to the results, it can be concluded that MgSO4 and CA, in an effective dose range, can be effective in controlling the neuropathic pain followed by vincristine, possibly through the modulation of antioxidant balance directed by CA or the NMDA and calcium receptor blocking properties of MgSO4.

The indole-alkaloid scytonemin, an ecologically and pharmaceutically important secondary metabolite, is exclusively biosynthesized by some cyanobacteria. Due to its photoprotective function and valuable antioxidant capacity, this cyano-sunscreen may be of great value for production of natural sunscreen in cosmetic and other pharmaceutical industries. As scytonemin is only produced by some cyanobacterial species, identification of novel strains and verification of synthesis induction factors are important research areas. In the present study, using the high-performance liquid chromatography and mass spectrometry analyses, scytonemin was characterized (UVλmax ) at 370 nm; m/z 545) in two filamentous cyanobacteria: Leptolyngbya mycodia and Phormidium sp. Under photosynthetic active radiation (PAR), L. mycodia revealed superior growth as well as scytonemin specific content of 0.0427 (Aλ/mg d.w.). As one of the physicochemical stressors on regulation of scytonemin biosynthesis, the role of UV irradiation in synthesis induction was examined. A remarkable change was observed on scytonemin specific content under PUAB regime (280-700 nm) compared to PAR (400–700 nm). UV-B (280–315 nm) significantly induced scytonemin synthesis up to 4.25 Aλ /mg d.w. while synthesis (2.31 Aλ/mg d.w.) to a lesser extent was observed under UV-A (315-400 nm). Moreover, present study confirmed the role of extracted scytonemin as an active antioxidant, indicating its strong radical scavenging (IC50=48.84%) with relatively high (61%) antioxidant rate at concentration of 200 μg/l. This is the first report on the UV-induced scytonemin biosynthesis by cyanobacterium L. mycodia and its remarkable antioxidant activity is of great value for future biotechnological research and development of natural sunscreens.

Neurotoxicity is an adverse effect of chemotherapy drugs on the central nervous system. Many studies have demonstrated that xanthine oxidase inhibitors prevent the formation of reactive oxygen species (ROS). The present study aimed to investigate the effects of allopurinol as an oxidase inhibitor on the learning and memory impairment induced by cisplatin. This study was conducted on 40 male Wistar rats, which were randomly divided into five groups, as follows: 1) control injected with saline (1 ml/kg/i.p); 2) cisplatin (5 mg/kg/once a week; i.p.); 3) allopurinol (ALP; 50 mg/kg/once a week; P.O.); 4) Cis+ALP 50 (cisplatin 5 mg/kg/i.p and allopurinol 50 mg/kg/once a week; P.O.) and 5) Cis+ALP 100 (cisplatin 5 mg/kg/i.p and allopurinol 100 mg/kg/once a week; P.O.). Drugs were administered for five weeks in all groups. The interval between administrations of drugs were half an hour. Morris water maze (MWM) was used to evaluate the memory and learning of the animals. The tissue brain concentrations of malondialdehyde (MDA), thiol, and superoxide dismutase (SOD) were measured using biochemical tests. According to the results, the cisplatin group had longer escape latency and shorter time spent and traveled pathway in the target quadrant compared to the control group. On the other hand, allopurinol treatment significantly reversed the results of the spatial memory test. The biochemical data indicated that cisplatin increased MDA concentration but decreased thiol and SOD activity compared to the control group. Administration of allopurinol decreased the MDA level but increased the thiol levels in the cortex and hippocampus tissues. Therefore, it was concluded that allopurinol could improve cisplatin-induced memory impairment by affecting the oxidative status of the brain tissue.

There is increasing evidence to suggest that the Lactobacilli species possess antioxidant activities, however, there are a few reports of optimization of solvent systems for the separation of their antioxidant compounds by thin-layer chromatography. In the current study, we explore the efficiency of four organic solvents (aqueous, methanol, ethyl acetate, and n-hexane) for the extraction of antioxidant materials from Lactobacillus supernatants. According to the results, methanol extraction significantly increased the antioxidant properties of Lactobacillus supernatants. In addition, the methanol extract of Lactobacillus supernatants was fractionated using thin-layer chromatography (TLC). A solvent system consisting of methanol/chloroform is a promising approach for TLC analysis of Lactobacillus supernatant. The partial purification of the antioxidant components using thin-layer chromatography demonstrated a drastic rise in the antibacterial and antioxidant properties in comparison to the crude methanol extract of the same sample. In this study, the TLC fractionation of Lactobacillus extracellular materials was described for the first time. Further isolation and purification are essential to identify these bioactive compounds.

The Human Immunodeficiency Virus (HIV) infection is a global health challenge that creates an urgent need to develop new therapeutic agents. In this work, a new group of quinazolinone derivatives were designed and synthesized and evaluated their anti-HIV activity. The antiviral assay revealed that some analogues inhibited HIV replication in the cell culture. A docking study using the later crystallographic data available for PFV integrase including its complexes with Mg2+ and dolutegravir, showed that the designed compounds bind into the active site of integrase enzyme such that both carbonyl groups chelate Mg2+ ions. Interestingly, all of the synthesized compounds were found to present no significant cytotoxicity at a concentration of 100 μM. According to the anti-HIV evaluation results, the compound 10f was found as the most active with the inhibition rate of 38%. Therefore, these compounds can provide a very good basis for the development of new anti-HIV agents.

The present study was conducted to investigate the hypoglycemic activity of 3,4,5-triphenyl-oxadiazole derivatives and its effects on liver, lung, and kidney function in streptozotocin (STZ)-induced diabetic rats. For this purpose, male Wistar rats were divided into four groups (n = 4). Diabetes was induced in four groups by a single dose of STZ at 65 mg/kg body weight, administrated intraperitoneal. After 28 days of treatment, fasting blood sugar (FBS) levels and other biochemical parameters such as cholesterol, triglycerides phosphorous, urea creatinine, etc. were measured. Also, the markers of liver and kidney function, such as urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase levels were determined. The study showed that the 3,4,5-triphenyl-oxadiazole derivatives at 100 mg/kg body weight had a significant antidiabetic activity after 28 days of treatment as the FBS levels decreased significantly while the serum insulin levels increased. Moreover, a significant decrease in the liver and kidney function markers in treated rats indicated the protective effect of the 3,4,5-triphenyl-oxadiazole derivatives against liver and kidney damage. The serum concentrations were normal in the control and the healthy group treated with these derivatives. The results of this study showed that both derivatives can regulate hyperglycemia and complications of diabetes.

Green tea, a common beverage, has several pharmacological effects. In this study, the amounts of phenolic compounds and epigallocatechin (EGC) were determined in an aqueous extract of green tea planted in Lahijan (a city in the north of Iran) by Folin-Ciocalteu method and HPLC, respectively. Antioxidant activity of the extract was measured by DPPH and the FRAP assays. Furthermore, its cytotoxic effect was investigated on HT-29 (colorectal cancer) and 3T3 (normal fibroblast) cell lines, after 24 and 48 h treatment by MTT method. Trypan blue dye exclusion measurement was also done on the HT-29 cells treated with the extract. The results have shown that each gram of the dried extract contains 283.6 ± 10.57 mg total phenolic content and 88.44 ± 1.85 mg EGC. The antioxidant activity of the extract measured by DPPH showed an EC50 value of 84.31 ± 4.14 μg/ml. In the FRAP test, the equivalent amount of Iron (Fe) was 4.45 mmol per g of the dried extract. The extract showed toxicity on the HT-29 cell line with an IC50 value of 82.45 ± 18.39 μg/ml after 48 h treatment. The data were confirmed by trypan blue dye exclusion test. Based on the results, adding green tea to the diet may have many health benefits.