Clues of HLAs, metabolic SNPs, and epigenetic factors in T cell-mediated drug hypersensitivity reactions.

Drug hypersensitivities are common reactions due to immunologic responses. They are of utmost importance because they may generate severe and fatal outcomes. Some drugs may cause Adverse Drug Reactions (ADRs), such as drug hypersensitivity reactions (DHRs), which can occur due to the interaction of intact drugs or their metabolites with Human Leukocyte Antigens (HLAs) and T cell receptors (TCRs). This type develops over a period of 24-72 h after exposure and is classified as type IV of DHRs. Acute generalized exanthematic pustulosis (AGEP), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are types of Severe Cutaneous Adverse Reactions (SCARs). In this review, we aim to discuss the types of ADRs, the mechanisms involved in their development, and the role of immunogenetic factors, such as HLAs in type IV DHRs, single-nucleotide polymorphisms (SNPs), and some epigenetic modifications, e.g., DNA/histone methylation in a variety of genes and their promoters which may predispose subjects to DHRs. In conclusion, development of promising novel in vitro or in vivo diagnostic and prognostic markers is essential for identifying susceptible subjects or providing treatment protocols to work up patients with drug allergies as personalized medicine.

Synergistic effects of Nepeta menthoides and Melissa officinalis aqueous extracts on reserpine-induced depressive-like behaviors in mice.

Nepeta menthoides Boiss. & Buhse and Melissa officinalis are extensively used in Persian medicine for the treatment of depression. Considering the active ingredients and main phenolic compounds of these plants and possible synergistic effects, this study examined the antidepressant and antioxidant activities of aqueous extract of N. menthoides (NM) and M. officinalis (MO) in reserpinized mice alone and combination. Mice were pretreated orally for 1-week with normal saline (10 ml/kg), fluoxetine (20 mg/kg), imipramine (10 mg/kg), NM (50-100-200-400 mg/kg), MO (150-350-550-750 mg/kg), and combination (NM 50 with MO 150 mg/kg). The behavioral changes were evaluated using forced swim, tail suspension, and open field tests, 24 hr after reserpine injection (4 mg/kg) on eighth day. The amounts of active components in the extracts and catalase (CAT) as a brain oxidative stress were measured with enzyme-linked immunosorbent assay. Data showed that this combination produced a synergistic action on behaviors and a significant increase in CAT activity. High-performance liquid chromatography results showed that rosmarinic acid contents in MO and NM were 6.42 ± 1.1 and 11.03 ± 2.16 mg/g of dried extract, respectively. Total flavonoid and phenolic contents of MO were higher than NM. The findings suggest that the present combination produces an antidepressant-like effect, which is possibly triggered by its antioxidant properties.