Mehdi Basaki

We evaluated the effects of artemisinin (ART) and L-carnitine (LC) on apoptosis and redox status of testicular tissue. Sixty mature male laboratory mice were randomly divided into six groups as follows. Control (saline + corn oil); Art50 (therapeutic ART) (50 mg/kg ART); Art250 (toxic ART) (250 mg/kg ART); Art50+L-car (370 mg/kg LC + 50 mg/kg ART); Art250+L-car (370 mg/kg LC + 250 mg/kg ART); and L-car (370 mg/kg LC). Drugs were given orally for one week. Therapeutic ART reduced the expression of the Bax without significant effect on Bcl2. Co-administration of LC and therapeutic ART reduced the expression of Bax and increased the expression of Bcl2. ART increased glutathione (GSH) and peroxidase activity. LC alone or together with ART also increased the GSH levels. Unlike the group receiving toxic ART, the number of apoptotic cells in the germinal epithelium was only slightly (~8%) higher than the control in the groups receiving therapeutic ART. Co-administration of LC and therapeutic ART reduced the number of apoptotic cells to the control level. Therapeutic ART not only did not induce apoptosis and oxidative stress but together with LC increased the antioxidant power of the testis by increasing the GSH level.

Hematopoiesis is a sensitive target of artemisinin (ART) and its derivatives, and hemolysis is one of their commonly reported side effects. l-carnitine (LC), an amino acid derivative involved in lipid metabolism, is beneficial for hematological parameters. Sixty adult laboratory mice were randomly divided into six groups. Group I (control) received saline and corn oil; groups II and III received therapeutic (50 mg/kg) and toxic (250 mg/kg) doses of ART, respectively; groups IV and V received 370 mg/kg LC along with the 50 and 250 mg/kg ART, respectively; and group VI received 370 mg/kg LC. Drugs were administered orally for 7 consecutive days. The erythrocyte glucose 6-phosphate dehydrogenase (G6PD), catalase (CAT), and peroxidase (POX) activity, and the reduced glutathione (GSH) level were assessed by colorimetric methods. ART reduced the G6PD activity both at therapeutic and toxic doses. The therapeutic dose of ART reduced the CAT activity and the GSH level, nonsignificantly. The toxic dose of ART reduced the CAT activity and increased the POX activity. LC reduced the G6PD, CAT, and POX activities and increased GSH level. The therapeutic dose of ART and LC showed synergy in reducing the G6PD activity. LC and ART combination reduced POX activity and increased GSH level without any significant effect on the CAT activity. Inhibition of G6PD may be a potentially new mechanism of ART action. Coadministration of LC with ART or following treatment with ART may have protective effects on erythrocytes.

Small heat shock proteins (SHSPs) are conserved proteins that participate in many cellular functions like preventing protein aggregation and stress response. However, their role in responding to nanoparticles (NPs) has not yet been explained. We used a chicken embryo model to investigate the effects of two different forms of iron oxide-NPs (IONPs) on the mRNA expression of HSPB1, HSPB5, HSPB8, and HSPB9 in cerebral tissue. Two hundred-ten fertilized eggs were randomly divided into seven groups (30 eggs/group; 10 eggs/replicate). Three groups received 100 ppm, 250 ppm, and 500 ppm of Fe₂O₃-NPs, respectively. Three other groups received 100 ppm, 250 ppm, and 500 ppm of Fe₃O₄-NPs, respectively, and one group remained untreated as a control. The NPs were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebrums were collected on day 20 for gene expression analyses. HSPB1, HSPB5, HSPB8, and HSPB9 were all expressed in both normal and IONPs exposed cerebrums. SHSPs tested were differentially expressed in response to various concentrations of IONPs. The highest expression levels in response to Fe₂O₃-NPs and Fe₃O₄-NPs were observed for HSPB5 and HSPB9, respectively. The greatest gene expression changes due to the Fe₂O₃-NPs and Fe₃O₄-NPs exposure observed for HSPB1 and HSPB5, respectively. The results suggest a protective cellular mechanism against IONPs through SHSPs and recommend that expression profiling of SHSPs be included in the study of nanotoxicity.

Ferroptosis is a form of cell death associated with iron‐dependent lipid peroxidation. We used a chicken embryo model to investigate if ferroptosis was implicated in the molecular mechanism underlying the potential effects of maternal exposure to iron oxide nanoparticles (IONPs) on the developing brain. One hundred and eighty fertilized eggs were randomly divided into six groups (30 eggs/group; 10 eggs/replicate). Groups I and II received maghemite (γ‐Fe₂O₃) NPs (MGMNPs), while groups III and IV received magnetite (Fe₃O₄) NPs (MGTNPs). Both MGMNP and MGTNP were administrated at the concentrations of 100 and 250 ppm. One group (placebo) received saline, and the other remained untreated (control). The compounds were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebral tissue were collected on day 20 for histopathological, biochemical and gene expression analyses. Total antioxidant capacity (TAC) and malondialdehyde (MDA) increased; glutathione peroxidase (GPX) expression and activity decreased in IONPs‐treated groups. Ferroptotic cells appeared in the cerebral tissue following exposure to the low dose of MGMNP and MGTNP. Oxidative stress and ferroptotic cells were more evident for MGMNP compared to MGTNP. The low dose of MGMNP and MGTNP induced more severe oxidative stress in the cerebral tissue. According to the results, maternal exposure to IONPs is associated with ferroptosis in the brain. This work could encourage future researches to investigate inhibitors of ferroptosis as a protective strategy against iron‐induced cell injuries and cell death.

Sudden death syndrome (SDS) is a stress related disease in broilers with no diagnostic clinical or necropsy findings. SDS is associated with ventricular tachycardia (VT) and ventricular fibrillation (VF); however, its pathogenesis is not precisely described at the molecular level. Dysfunction of ryanodine receptor 2 (RYR2), that control rapid release of Ca²⁺ from sarcoplasmic reticulum (SR) into the cytosol during muscle contraction, have been attributed to the VT and sudden cardiac death (SCD) in human patients with structurally normal heart but there is no report describing abnormalities in RYR2 in the diseased broilers. In order to advance our knowledge on the molecular mechanisms predisposing broilers to fatal arrhythmia the present study was conducted to determine the occurrence of possible mutations and changes in expression level of chicken RYR2 gene (chRYR2) in broilers that died from SDS.‏ An increase in mRNA expression level and nine novel point mutations in chRYR2 were found in relation to SDS. In conclusion, susceptibility to lethal cardiac arrhythmia in SDS may be associated with specific changes in intracellular Ca²⁺ cycling components such as RYR2 due to mutation and dysregulation. Finding the probable association of SDS with gene defects can be applied to select for chickens with lower susceptibility to SDS and decrease the poultry industry losses due to SDS mortality.