RESUMEN
SUMMARY: Osteoporosis is a bone condition marked by a loss of bone mass and a disruption of bone microarchitecture. Men lose bone density as they age, resulting in brittle bones. The loss of free testosterone is one of the key factors. The objective of present study was to evaluate Allolobophora caliginosa extract (AcE) for its anti-osteoporotic and antiapoptotic activity in orchiotomized rat model at two different dose levels. Twenty eight male rats were divided into two groups. The first group represented sham operated rats while the second group underwent bilateral orchidectomy (OCX). After one week of recovery from orchidectomy surgery, the second group was randomly subdivided into 3 subgroups. The first OCX subgroup was administered orally distilled water daily for 10 weeks. The other two OCX subgroups were administered AcE (100 or200 mg/kg body weight/day) orally for 10 weeks. Orchiectomy induces remarkable loss of the cortical as well as trabecular bone loss; which, could be counterbalanced by Allolobophora caliginosa extract (AcE) that prevented cortical as well as trabecular bone loss. Allolobophora caliginosa extract (AcE) at Dose 200 mg/kg/day was found to be effective at a highly significant level in osteoporotic bone, as determined by histological images and immunohistochemical study, where Dose (100 mg/kg/day) was found to be moderately significant.In the present study, it is suggested that AcE may inhibit steroid-induced osteoblasts apoptosis, potentially via upregulation of Bcl-2 and downregulation of caspase-3. Allolobophora caliginosa extract demonstrates anti-apoptotic and anti-oxidant properties. Therefore, AcE may be used for the prevention of steroid-induced bone damage.
RESUMEN: La osteoporosis es una afección ósea caracterizada por una pérdida de masa ósea y una alteración de la microarquitectura ósea. Los hombres pierden densidad ósea a medida que envejecen, lo que resulta en huesos quebradizos. La pérdida de testosterona libre es factor clave en este proceso. El objetivo del presente estudio fue evaluar el extracto de Allolobophora caliginosa (AcE) debido a su actividad antiosteoporótica y antiapoptótica en un modelo de rata orquiectomizadas con dos niveles de dosis diferentes. Se dividieron veintiocho ratas macho en dos grupos. El primer grupo incluyó ratas con operación simulada, mientras que el segundo grupo se sometió a orquidectomía bilateral (OCX). Después de una semana de recuperación de la orquidectomía, el segundo grupo fue subdividido en 3 subgrupos. Al primer subgrupo de OCX se administró diariamente agua destilada por vía oral durante 10 semanas. Los otros dos subgrupos de OCX se administraron por vía oral AcE (100 o 200 mg / kg de peso corporal / día) durante 10 semanas. La orquidectomía induce una pérdida notable del hueso cortical y trabecular; el cual podría ser contrarrestado por el extracto de Allolobophora caliginosa (AcE) que previno la pérdida de hueso tanto cortical como trabecular visualizado en imágenes histológicas y estudio inmuno- histoquímico, donde se encontró que la dosis (100 mg / kg / día) era moderadamente significativa. En el presente estudio, se sugiere que la AcE puede inhibir la apoptosis de los osteoblastos inducida por esteroides, potencialmente a través de la regulación al alza de Bcl 2 y la regulación a la baja de caspasa 3. El extracto de Allolobophora caliginosa demuestra propiedades anti apoptóticas y antioxidantes. Por lo tanto, AcE puede usarse para la prevención del daño óseo inducido por esteroides.
Asunto(s)
Animales , Masculino , Ratas , Oligoquetos , Osteoporosis/tratamiento farmacológico , Extractos de Tejidos/administración & dosificación , Orquiectomía/efectos adversos , Osteoporosis/etiología , Osteoporosis/prevención & control , Extractos de Tejidos/farmacología , Huesos/efectos de los fármacos , Inmunohistoquímica , Ratas Wistar , Apoptosis/efectos de los fármacosRESUMEN
Levamisole (LEVA) and garlic are prevalent immunomodulators in humans and animals. Therefore, the present study aimed to examine the immunomodulatory effects of LEVA and garlic oil (GO) alone or in combination on the immune response of Wistar rats. A total of 24 male Wistar rats were allocated into four equal groups: Control group, which was given ad libitum access to food and water; and groups 24, which were orally administered LEVA [2.5 mg/kg body weight (BW) every 2 days], GO, (5 ml/kg BW daily), or LEVA plus GO, respectively for 4 consecutive weeks. Serum immunoglobulin (Ig)G and IgM levels were measured using a radial immunodiffusion assay. Serum cytokine levels, including interferon (IFN)-γ, interleukin (IL)-5 and tumor necrosis factor (TNF)-α, were measured using enzymelinked immunosorbent assay kits. Total blood counts were measured automatically using a cell counter. Serum lysozyme enzymatic activity was determined by measuring the diameters of the zones of clearance relative to lysozyme. Immunohistochemical detection of CD4 and CD8 was carried out using the streptavidin-biotin-peroxidase method. Furthermore, the mRNA expression levels of IL4, IL5 and IL12 were measured in the leukocytes and thymus gland by semi-quantitative polymerase chain reaction. The results revealed that LEVA increased serum levels of IFNγ, IL5 and TNFα cytokines, whereas coadministration of LEVA and GO decreased the stimulatory action of LEVA alone. LEVA and GO alone increased the serum levels of IgG, IgM and total blood cell counts, and coadministration of GO and LEVA inhibited the effects of LEVA. At the cellular level, in the spleen, LEVA increased immunoreactivity of CD4 and CD8, whereas coadministration of GO with LEVA decreased this strong expression. At the molecular level, in leukocytes, LEVA upregulated the mRNA expression levels of IL2, IL4 and IL5, whereas GO alone downregulated mRNA expression. Coadministration of GO with LEVA inhibited the LEVAinduced upregulation of IL2, IL4 and IL5 mRNA expression. In the thymus, both LEVA and GO upregulated the mRNA expression levels of IL4 and IL5, whereas LEVA alone did not affect IL12 mRNA expression. Coadministration of GO with LEVA inhibited LEVAinduced upregulation of IL4 and GOinduced upregulation of IL12 expression, and had an additive upregulatory effect on IL5 expression. In conclusion, LEVA stimulated Thelper (Th)1 cytokines, whereas GO stimulated a Th2 response, and coadministration of GO with LEVA inhibited the stimulatory effects of LEVA and balanced the Th1/Th2 response.