Effect of mouse sex on pharmacological investigations

J. Pharm. Pharmacogn. Res., vol. 8, no. 6, pp. 569-579, November-December 2020.

Original Article

Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model

[Efecto de las diferencias sexuales en las actividades antinociceptiva, antipirética, hipoglucemia, hepatoprotectora y antidiarreica en modelo de ratones]

Irin Karim#, Roni Roy#, Md Rafiul Hoque, Sazzad Hosen, Tanaya Bhowmik, Israt Jahan Liya, Afroza Akter, Mohammad Anwarul Basher

Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali-3814, Bangladesh.
#These two authors contributed equally.

Abstract

Context: The use of animal models is a longstanding practice in biological research. Among different models, the mouse is the most widely used and accepted model. In designing the mouse model, a male mouse is generally preferred over a female to avoid the effect of changing hormonal state in females. However, it is not known whether mouse sex affects all experiments.

Aims: To determine the effect of mouse sex on pharmacological responses in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal experiments.

Methods: Antinociceptive study was performed by three different experiments. An antipyretic experiment was performed by yeast induced hyperthermia test. The effect on hypoglycemic response was assessed by an oral glucose tolerance test. The effect on the hepatoprotective study was evaluated by carbon tetrachloride-induced liver damage. The antidiarrheal study was conducted by a castor oil-induced diarrhea test.

Results: Antinociceptive studies demonstrated mixed effects. Hot plate test showed significant differences; the licking test showed variation only in the late phase, while no significant variation was observed. In the antipyretic experiment, female mice showed higher body temperature in both control and standard that varied significantly with male mice. Hypoglycemia and hepatoprotective tests did not show significant variation between sexes; however, liver enzymes levels were found higher in males while the percentage liver weight was higher in females. In the antidiarrheal test, the male mouse was observed to have higher responses than the female.

Conclusions: Antinociceptive and antipyretic investigations should be performed separately on both male and female mice. On the other hand, hypoglycemic, hepatoprotective and antidiarrheal tests can be conducted on any mouse sex, and findings on particular sex can be extrapolated to the opposite sex.

Keywords: drug discovery; sex dimorphism; Swiss albino mice.

Resumen

Contexto: El uso de modelos animales es una práctica de larga data en la investigación biológica. Entre los diferentes modelos, el ratón es el modelo más utilizado y aceptado. Al diseñar el modelo de ratón, generalmente se prefiere un ratón macho a una hembra para evitar el efecto del cambio de estado hormonal en las hembras. Sin embargo, no se sabe si el sexo del ratón afecta a todos los experimentos.

Objetivos: Determinar el efecto del sexo del ratón sobre las respuestas farmacológicas en experimentos antinociceptivos, antipiréticos, hipoglucémicos, hepatoprotectores y antidiarreicos.

Métodos: Se realizaron experimentos para demostrar efectos anti-nociceptivo (tres experimentos diferentes), antipirético (hipertermia inducida por levaduras), hipoglucémico (prueba de tolerancia a la glucosa oral), hepatoprotector (daño hepático inducido por tetracloruro de carbono) y antidiarreico (diarrea inducida por aceite de ricino).

Resultados: Los estudios antinociceptivos demostraron efectos mixtos. La prueba de la placa caliente mostró diferencias significativas; la prueba de lamido mostró variación solo en la fase tardía, mientras que no se observó variación significativa. En el experimento antipirético, las hembras mostraron una temperatura corporal más alta tanto en el control como en el estándar que varió significativamente con los ratones machos. Las pruebas de hipoglucemia y hepatoprotección no mostraron variación significativa entre sexos; sin embargo, los niveles de enzimas hepáticas se encontraron más altos en los machos mientras que el porcentaje de peso del hígado fue más alto en las hembras. En la prueba antidiarreica, se observó que el ratón macho tenía respuestas más altas que la hembra.

Conclusiones: Las investigaciones antinociceptivas y antipiréticas debían realizarse por separado en ratones machos y hembras. Por otro lado, las pruebas hipoglucémicas, hepatoprotectoras y antidiarreicas podrían realizarse en cualquier sexo de ratón, y los hallazgos sobre un sexo particular se pueden extrapolar al sexo opuesto.

Palabras Clave: dimorfismo sexual; investigación en medicamento; ratones albinos suizos.

Download the PDF file .

Citation Format: Karim I, Roy R, Hoque MR, Hosen S, Bhowmik T, Liya IJ, Akter A, Basher MA (2020) Effect of sex differences in antinociceptive, antipyretic, hypoglycemia, hepatoprotective and antidiarrheal activities in mice model. J Pharm Pharmacogn Res 8(6): 569–579.
References

Afonso-Pereira F, Dou L, Trenfield SJ, Madla CM, Murdan S, Sousa J, Veiga F, Basit AW (2018) Sex differences in the gastrointestinal tract of rats and the implications for oral drug delivery. Eur J Pharm Sci 115: 339–344.

Awouters F, Niemegeers CJ, Lenaerts FM, Janssen PA (1978) Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis. J Pharm Pharmacol 30: 41–45.

Ballou LR, Botting RM, Goorha S, Zhang J, Vane JR (2000) Nociception in cyclooxygenase isozyme-deficient mice. Proc Natl Acad Sci USA 97: 10272–10276.

Balmain A, Harris C (2000) Carcinogenesis in mouse and human cells: parallels and paradoxes. Carcinogenesis 21: 347–371.

Beery AK, Zucker I (2011) Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35: 565–572.

Berkenkopf JW, Weichman BM (1988) Production of prostacyclin in mice following intraperitoneal injection of acetic acid, phenylbenzoquinone and zymosan: its role in the writhing response. Prostaglandins 36: 693–709.

Craft RM (2003) Sex differences in opioid analgesia: “From mouse to man”. Clin J Pain 19: 175–186.

Cragg GM, Kingston DG, Newman DJ (2011) Anticancer agents from natural products. CRC press.

DeHaven-Hudkins D, Burgos LC, Cassel J, Daubert J, DeHaven R, Mansson E, Nagasaka H, Yu G, Yaksh T (1999) Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther 289: 494–502.

Dubuisson D, Dennis SG (1977) The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 4: 161–174.

European Union (2020) Report of European Union, The Statistics on the Number of Animals Used for Experimental and Other Scientific Purposes.

Fabricant DS, Farnsworth NR (2001) The value of plants used in traditional medicine for drug discovery. Environ Health Perspect 109: 69–75.

Fatehi-Hassanabad Z, Jafarzadeh M, Fafehi M, Razavi-Tossi MT (2005) Sex affects the feeling of pain in the mice, possible involvement of nitric oxide. DARU J Pharm Sci 13: 116–119.

Field M, Rao MC, Chang EB (1989) Intestinal electrolyte transport and diarrheal disease. N Engl J Med 321: 800–806.

Gregory MS, Duffner AL, Hahn LE, Hsin-Hsiung T, Faunce ED, Kovacs JE (2000) Differential production of prostaglandin E2 in male and female mice subjected to thermal injury contributes to the gender difference in immune function: possible role for 15-hydroxyprostaglandin dehydrogenase. Cell Immunol 205: 94–102.

Kaikaew K, Steenbergen J, van Dijk TH, Grefhorst A, Visser JA (2019) Sex difference in corticosterone-induced insulin resistance in mice. Endocrinology 160: 2367-2387.

Kaur N, Kishore L, Singh R (2016) Attenuating diabetes: What really works? Curr Diabetes Rev 12: 259–278.

Koster R, Anderson M, de Beer EJ (1959) Acetic acid for analgesic screening. Fed Proceed 18: 412–417.

Linhart O, Obreja O, Kress M (2003) The inflammatory mediators serotonin, prostaglandin E2 and bradykinin evoke calcium influx in rat sensory neurons. Neuroscience 118: 69–74.

Lwoff A (1971) Protoza to bacteria and viruses-fifty years with microbes. Annu Rev Microbiol 25: 1–27.

Mascolo N, Izzo AA, Barbato F, Capasso F (1993) Inhibitors of nitric oxide synthetase prevent castor-oil-induced diarrhoea in the rat. Br J Pharmacol 108: 861–864.

Mia S, Roy R, Akter A, Barek MA, Basher MA (2019) Hypoglycemic effect of leaf extract of Fimbristylis miliacea in mice model. Clin Phytoscience 5: 26.

Pace S, Rossi A, Krauth V, Dehm F, Troisi F, Bilancia R, Weinigel C, Rummler S, Werz O, Sautebin L (2017) Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation. Sci Rep 7: 3759.

Pathan H, Williams J (2012) Basic opioid pharmacology: An update. Br J Pain 6: 11–16.

Shore R, Björne H, Omoto Y, Siemiatkowska A, Gustafsson J-Å, Lindblad M, Holm L (2017) Sex differences and effects of oestrogen in rat gastric mucosal defence. World J Gastroenterol 23: 426–436.

Siegmund E, Cadmus R, Lu G (1957) A method for evaluating both non-narcotic and narcotic analgesics. Proc Soc Exp Biol Med 95: 729–731.

Sorge RE, Mapplebeck JCS, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin J-S, Sotocinal SG, Chen D, Yang M, Shi XQ, Huang H, Pillon NJ, Bilan PJ, Tu Y, Klip A, Ji R-R, Zhang J, Salter MW, Mogil JS (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18: 1081–1083.

Stitt JT (1973) Prosaglandin E1 fever induced in rabbits. J Physiol 232: 163–179.

Suzuki Y, Nakahara K, Ensho T, Murakami N (2017) Sex difference of hyperinsulinemia in the C57BL/6J-Daruma (obese) mouse. J Vet Med Sci 79: 1284–1293.

Tomazetti J, Avila DS, Ferreira AP, Martins JS, Souza FR, Royer C, Rubin MA, Oliveira MR, Bonacorso HG, Martins MA, Zanatta N, Mello CF (2005) Baker yeast-induced fever in young rats: characterization and validation of an animal model for antipyretics screening. J Neurosci Methods 147: 29–35.

Vecchio I, Tornali C, Bragazzi NL, Martini M (2018) The Discovery of Insulin: An Important Milestone in the History of Medicine. Front Endocrinol (Lausanne) 9: 613.

Wald C, Wu C (2010) Of mice and women: The bias in animal models. Science 327(5973): 1571–1572.

Woo H, Okamoto S, Guiney D, Gunn JS, Fierer J (2008) A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice. PLoS One 3: e1603.

Woolfe G, MacDonald AD (1944) The evaluation of the analgesic action of pethidine hydrochloride (demerol). J Pharmacol Exp Ther 80: 300–307.

Yoshitake I, Ohishi E, Kubo K (1991) Hepatoprotective effects of 1-[(2-thiazolin-2-yl)-amino]acetyl-4-(1,3-dithiol-2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) in various experimental liver injuries. Jpn J Pharmacol 57: 127–136.

© 2020 Journal of Pharmacy & Pharmacognosy Research (JPPRes)