Risperidone (Synonyms: Apexidone, Psychodal, R 64766)

Cell lines

MC3T3-E1 cells

Preparation Method

MC3T3-E1 subclone 14 was cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplement with 10% fatal bovine serum, and 1% penicillin-streptomycin antibiotics. When cells were confluent to 80–90%, serial passage was performed. Cells were washed twice with D-Hank’s solution and digested with 1ml of 0.25% trypsinEDTA. Next, 10×culture medium was added for stopping digestion and a few T25 flasks were used for reseeding. 10mM Risperidone stock was prepared in DMSO solution. To assess the effects of Risperidone on MC3T3-E1 cell proliferation, CCK-8 kit was used to detect cell proliferation rate in an empty group (only medium, no cells), control group (with medium and cells, but no Risperidone), and experimental group (with medium, cells, and different doses of Risperidone). Briefly, 2×10³ MC3T3-E1 cells per well were seeded in a 96-well plate and incubated for 24h at 37°C in 5% CO₂. When cells were 80–90% confluent, the culture medium was replaced with fresh medium with no serum. Subsequently, 10, 50, 100, and 200μM Risperidone was added to the medium in duplicate wells. Cells were cultured for 48h. CCK-8 reagents were added into 96-well plates and incubated for 4h. Absorbance (AB) was measured at 450nm wavelength. Cell viability (%) = [AB of experimental group – AB of empty group] / [AB of control group – AB of empty group] 100%.

Reaction Conditions

10-200μM; 48h

Applications

Treatment of MC3T3-E1 cells with Risperidone inhibited cell proliferation in a dose-dependent manner.

Animal models

C57BL/6J mice

Preparation Method

C57BL/6J mice were continually fed an HFD diet (diet 592Z, containing 20.4% of protein and modified laboratory with 35.5% lard, with 4.5kcal/g metabolizable energy; PMI Nutrition International) for 10 weeks. To establish obesity, our mice were administered the HFD for 10 weeks longer than the typical duration (i.e., 4 weeks). The groups were subsequently separated to form two subgroups: one receiving 1mg/kg oral Risperidone and the other (control group) receiving saline through daily gavage for the final 56 days of the diet period. During the experiment, mice were separately kept in microisolation cages placed on racks ventilated by air filtered by high-efficiency particulate air filters under temperature and humidity controlled at 22±1°C and 55%±5%, respectively, under a 12:12h light/dark cycle, all with free water and food access. We monitored body weight and food intake on a weekly basis from experiment initiation. At the end of the experiment, we euthanized all mice and harvested their blood and various tissues for further analysis. Furthermore, we evaluated the impacts of orally administered Risperidone on the weight, food intake, adipocyte content, biochemical changes, blood glucose level, fatty liver scores, endocrine profiles, hepatic lipogenesis, insulin signaling expression, and renal pathology of the mice.

Dosage form

1mg/kg/day; p.o.; 56 days

Applications

Risperidone increased body weight, fatty liver scores, serum ALT/AST, triglycerides, BUN, and creatinine, decreased GLUT4 expression and Akt phosphorylation, and induced renal inflammation in high-fat diet-fed C57BL/6J mice.

References:
[1]Zheng L, Yang L, Zhao X, Long N, Li P, Wang Y. Effect of risperidone on proliferation and apoptosis of MC3T3-E1 cells. Braz J Med Biol Res. 2019;52(3):e8098.
[2] Tsai HP, Hou PH, Mao FC, et al. Risperidone Exacerbates Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Renal Impairment in Obese Mice. Int J Mol Sci. 2021;22(1):409.