Effects of Coriandrum sativum on distant organ inflammation and apoptosis due to liver ischemia/reperfusion injury.

Liver ischemia/reperfusion (IR) often affects distant organs, such as small intestine, kidney, and lung. Coriandrum sativum (CS) has an antioxidant and anti-inflammatory effect on liver damage. The aim of this study was to investigate the anti-inflammatory and antiapoptotic effects of CS extract on small intestine, lung, and kidney after the liver IR injury. Small intestine, lung, and kidney tissues were evaluated and scored in terms of cell degeneration, inflammation, and congestion, as well as caspase-3 (Cas-3) and cluster of differentiation 31 (CD31) immunostainings were carried out. Renal enzymes, creatinine and urea levels were measured biochemically in serum. After IR, a decrease in villi size, diffuse degeneration, epithelial cell shedding and extensive congestion in the capillaries were observed. Meanwhile, the number of degenerated villi and congestion decreased in the IR+CS group. Due to IR, increased congestion was detected in the interalveolar septum of the lungs and in the capillaries between the kidney tubules. It was also observed that the positively stained cells with Cas-3 and CD31 were increased in the lung, kidney, and small intestine tissues of the IR group, and decreased in the IR+CS group. Kidney enzymes, urea and creatinine levels were significantly increased in the IR group and decreased in the IR+CS group. In conclusion, it was observed that liver IR caused changes in distant organs, especially in the small intestine, lung, and kidneys. Damaging effects of IR as well as apoptosis and inflammation were found to be decreased in the groups treated with CS.

Protein Scaffold-Based Multimerization of Soluble ACE2 Efficiently Blocks SARS-CoV-2 Infection In Vitro and In Vivo.

Soluble ACE2 (sACE2) decoys are promising agents to inhibit SARS-CoV-2, as their efficiency is unlikely to be affected by escape mutations. However, their success is limited by their relatively poor potency. To address this challenge, multimeric sACE2 consisting of SunTag or MoonTag systems is developed. These systems are extremely effective in neutralizing SARS-CoV-2 in pseudoviral systems and in clinical isolates, perform better than the dimeric or trimeric sACE2, and exhibit greater than 100-fold neutralization efficiency, compared to monomeric sACE2. SunTag or MoonTag fused to a more potent sACE2 (v1) achieves a sub-nanomolar IC50 , comparable with clinical monoclonal antibodies. Pseudoviruses bearing mutations for variants of concern, including delta and omicron, are also neutralized efficiently with multimeric sACE2. Finally, therapeutic treatment of sACE2(v1)-MoonTag provides protection against SARS-CoV-2 infection in an in vivo mouse model. Therefore, highly potent multimeric sACE2 may offer a promising treatment approach against SARS-CoV-2 infections.

Parabiosis Improves Endothelial Dysfunction in Aged Female Mice.

INTRODUCTION: The study aims to investigate the effect of parabiosis method on endothelial dysfunction in naturally aging mice and determine the time projections for predicted improvement in the mentioned target group. METHODS: The balb/c mice were separated into six groups, these being; isochronic old, heterochronic old (HP-O), isochronic young, heterochronic young, young control, and old control. After parabiosis protocol, animals were sacrificed at the third, fifth, seventh, and ninth weeks, and their thoracic aortas were isolated. The vasodilatation and vasoconstriction responses of the vessels were detected using potassium chloride and phenylephrine, acetylcholine (ACh), and sodium nitroprusside. RESULTS: Aging had a significant decreasing effect on maximum ACh relaxation responses (P < 0.01). However, in the HP-O group, the maximum ACh relaxation response in the third week was significantly lower (P < 0.05), but this effect disappeared in the ninth week. Maximum phenylephrine contraction responses were lower in the heterochronic parabiosis group (P < 0.05). CONCLUSIONS: ACh responses increased at the end of the ninth week in the HP-O group, therefore, the parabiosis model may have an improving effect on endothelial dysfunction seen in aging.

Effect of kefir on increased apoptosis in liver and kidney in cisplatin toxicity / Efecto del kéfir sobre el aumento de la apoptosis en el hígado y los riñones en la toxicidad del cisplatino

SUMMARY: Cisplatin is a chemotherapeutic agent inducing liver and kidney damage. In this study, we intended to investigate the impact of kefir beverage, an essential probiotic and functional food, on liver and kidney damage induced by cisplatin. Wistar albino rats were divided into four groups: Control, Cisplatin (single dose of 7 mg/kg, intraperitoneal), Kefir (2 ml/d, 7 d, oral gavage), and Cisplatin+Kefir (CK). At the end of day 7, animals were euthanized. Blood, kidney, and liver tissue samples were collected. For both tissues, biochemically ALT, AST, Urea, Creatine; histomorphologically, hematoxylin-eosin, Masson's Trichrome, and immunohistochemical staining of caspase-3, a marker of apoptosis, were performed. Serum urea and creatinine levels of the Cisplatin group were significantly higher than the Control group (p<0.05). In the CK group, kefir consumption decreased urea and creatinin levels approached to Control and Kefir groups. Cisplatin resulted in higher ALT and AST activities, indicating hepatocellular damage, compared to the Control group (p<0.05). Kefir consumption decreased ALT activities approached to both the Control and Kefir group. Histomorphological observations were in agreement biochemical results. In liver and kidney tissues, structural damage was observed with an increase in collagen fibers in the Cisplatin group, and Caspase-3 activity was immunohistochemically higher than in the other groups. In the CK group, collagen fiber increase, structural damage, and Caspase-3 activities were less than in the Cisplatin group. Kefir consumption alleviated liver and kidney damage. However, more research is required to understand such effect of kefir better.

RESUMEN: El cisplatino es un agente quimioterapéutico que induce daño hepático y renal. En este estudio, intentamos investigar el efecto del kéfir, un alimento funcional y probiótico esencial, en el daño hepático y renal inducido por el cisplatino. Se dividieron ratas albinas Wistar en cuatro grupos: control, cisplatino (dosis única de 7 mg/kg, intraperitoneal), kéfir (2 ml/día, 7 días, sonda oral) y cisplatino + kéfir (CK). Al final del día 7, los animales fueron sacrificados. Se recolectaron muestras de sangre, riñón y tejido hepático. Se determinó ALT, AST, Urea y Creatina; Para el análisis histomorfológico, se realizaron tinciones con hematoxilina-eosina, tricrómico de Masson y para inmunohistoquímica, caspasa-3, un marcador de apoptosis. Los niveles séricos de urea y creatinina del grupo de cisplatino fueron significativamente más altos que los del grupo de control (p<0,05). En el grupo CK, el consumo de kéfir disminuyó los niveles de urea y creatinina acercándose a los grupos Control y Kéfir. El cisplatino resultó en actividades más altas de ALT y AST, lo que indica daño hepatocelular, en comparación con el grupo Control (p<0.05). El consumo de kéfir disminuyó las actividades de ALT tanto en el grupo Control como en el de Kéfir. Las observaciones histomorfológicas coincidieron con los resultados bioquímicos. En tejidos hepáticos y renales se observó daño estructural con aumento de fibras colágenas en el grupo de Cisplatino, y la actividad de Caspasa-3 fue inmunohistoquímicamente mayor que en los otros grupos. En el grupo de CK, el aumento de las fibras colágenas, el daño estructural y las actividades de Caspasa-3 fueron menores que en el grupo Cisplatino. El consumo de kéfir mejoró el daño hepático y renal. Sin embargo, se requiere más investigación para comprender mejor el efecto del kéfir.

Comparison of age-related anti Müllerian hormone, inhibin-b levels and follicle reserve in rat ovarium / Comparación de la hormona anti-mülleriana relacionada con la edad, los niveles de inhibina-b y la reserva folicular en el ovario de rata

SUMMARY: Anti-Müllerian hormone (AMH) and Inhibin B (INHB) in the glycoprotein structure are members of the transforming growth factor β family and expressed by granulosa cells from puberty. AMH is a factor that increases the life span of small developing follicles. For this reason, it is widely used to determine the ovarian reserve and age. Inhibin-B secreted from granulosa cells plays a role in regulation of the Follicle Stimulating Factor (FSH) and determination of the follicle diameter. There are few studies on the effect of these two age-related hormones on ovarian histology in rats. In this study, AMH and INHB expression in ovarian tissues of female rats of different age groups, their relationship with ovarian structure and folliculogenesis were examined histologically and biochemically. Wistar Albino rats were used in the study and a total of 3 groups were formed. The ovaries of rats in the pre-oestrous period were collected, and follicle count was performed on tissue sections in batches. Expression of AMH in the follicles was identified immunohistochemically. In serum, AMH and INHB levels were assessed by ELISA method and their significance was evaluated statistically. Results from light microscopic examination determined that AMH was expressed from the granulosa cells of developing follicles. INHB expression during the prepubertal period and AMH had a protective effect on the ovarian reserve and the number of developing follicles, respectively.

RESUMEN: La hormona antimülleriana (AMH) y la inhibina B (INHB) en la estructura de la glicoproteína son miembros de la familia del factor de crecimiento transformante β y se expresan en las células de la granulosa desde la pubertad. La AMH es un factor que aumenta la vida útil de los pequeños folículos en desarrollo. Por este motivo, se utiliza frecuentemente para determinar la reserva ovárica y la edad. La inhibina B secretada por las células de la granulosa tiene un rol en la regulación del factor estimulante de (FSH) y en la determinación del diámetro del folículo. Hay pocos estudios sobre el efecto de estas dos hormonas relacionadas con la edad en la histología ovárica en ratas. Se examinaron histológica y bioquímicamente la expresión de AMH e INHB en tejidos ováricos de ratas hembras de diferentes grupos de edad, su relación con la estructura ovárica y la foliculogénesis. Se utilizaron ratas Wistar Albino en el estudio y se formaron 3 grupos. En los ovarios de ratas en el período preestro se realizó el recuento de folículos en secciones de tejido. La expresión de AMH en los folículos se identificó inmunohistoquímicamente. En suero, los niveles de AMH e INHB se evaluaron mediante el método ELISA y su importancia se evaluó estadísticamente. Los resultados del examen con microscopio óptico determinaron que la AMH se expresaba a partir de las células de la granulosa de los folículos en desarrollo. La expresión de INHB durante el período prepuberal y AMH tuvo un efecto protector sobre la reserva ovárica y el número de folículos en desarrollo, respectivamente.

Effects of Corchorus olitorius and protacatechuic acid on diabetic rat testis tissue / Efectos de Corchorus olitorius y ácido protocatéquico en el tejido testicular de rata diabética

SUMMARY: The aim of this study is to investigate the effects of Protocatechuic acid and Corchorus olitorius on streptozotocin (STZ) induced diabetic rat testis tissue. Randomly selected Wistar Albino rats were divided into five groups as; Diabetes Mellitus, Diabetes Mellitus treated with Corchorus Olitorus (STZ+CO), Diabetes Mellitus treated with Protacatechuic acid (STZ+PCA), Corchorus olitorius (CO), Protocatechuic acid (PCA) and Control. Diabetic model was generated by intraperitoneal injection of 60 mg/kg Streptozotosin. After 48 hours of the STZ injection, blood samples were collected from tail vein in order to measure blood glycose levels. Over 250 mg/dL accepted as diabetic subjets and fed with 250 mg/kg Corchorus olitorius or 20 mg/kg PCA by oral gavage for three weeks. At the end of the experiment, right testes were removed and fixed in 10 % neutral formaldehyde for paraffine embedding. Sections were stained by HE, Masson trichrome, PAS and TUNEL for microscopic evaluation. Control, PCA-only and Corchorus olitorius-only treated group testes tissues showed a normal tissue organization, when degeneration in seminiferous tubules, the vacuolization, seperations in spermatogenic cell series, outpouring of cell groups in the lumen, vesicular body formation, liquid accumulation in the interstitial region and edema were observed in STZ induced diabetic models and untreated groups. Besides, higher amount of TUNEL (+) stained cells were determined in STZ group. On the other hand, blood glucose level and number of TUNEL (+) stained cells were decreased as a result of PCA and Corchorus olitorius treatment. Because of the reduction of blood glucose level and apoptotic cell numbers, PCA and Corchorus olitorius decreace the complications of diabetes mellitus induced rat testis.

RESUMEN: El objetivo de este estudio fue investigar los efectos del ácido protocatéquico y Corchorus olitorius sobre el tejido testicular de rata diabética inducida por estreptozotocina (STZ). Las ratas Wistar Albino fueron seleccionadas al azar y se dividieron en cinco grupos; Diabetes Mellitus, Diabetes Mellitus tratada con Corchorus olitorius (STZ + CO), Diabetes Mellitus tratada con ácido protocatéquico (STZ + PCA), Corchorus olitorius (CO), ácido protocatéquico (PCA) y Control. El modelo diabético se generó por inyección intraperitoneal de 60 mg/kg de estreptozotosina. Después de 48 horas de la inyección de STZ, se recogieron muestras de sangre de la vena de la cola para medir los niveles de glucosa. Niveles mayores a 250 mg/dL fueron considerados como especímenes diabéticos y alimentados con Corchorus olitorius de 250 mg/kg o PCA de 20 mg/kg por sonda oral durante tres semanas. Al final del experimento, se extirparon los testículos derechos y se fijaron en formaldehído neutro al 10 % para la inclusión en parafina. Las secciones se tiñeron con HE, tricromo de Masson, PAS y TUNEL para evaluación microscópica. Los tejidos de los testículos de los grupos control, tratados solo con PCA y con Corchorus olitorius mostraron una organización tisular normal. En cambio en modelos diabéticos inducidos por STZ y grupos no tratados se observó degeneración en los túbulos seminíferos, vacuolización, separaciones en series de células espermatogénicas, efusión de grupos celulares en la luz, formación del cuerpo vesicular, acumulación de líquido en la región intersticial y edema. Además, se determinó una mayor cantidad de células teñidas con TUNEL (+) en el grupo STZ. Por otro lado, el nivel de glucosa en sangre y el número de células teñidas con TUNEL (+) disminuyeron como resultado del tratamiento con PCA y Corchorus olitorius. Debido a la reducción del nivel de glucosa en sangre y el número de células apoptóticas, se observó que PCA y Corchorus olitorius disminuyen las complicaciones de los testículos de rata inducidos por diabetes mellitus.

Evaluation of the Effect of Topical Hypericum perforatum Oil on Excisional Palatal Wound Healing in Rabbits.

Aim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.

Investigation of potential genomic biomarkers for obesity and personalized medicine.

Obesity, as a global health issue, is a complex metabolic syndrome and its association with many chronic diseases. The pathology of obesity results from an interaction of psychological, environmental and variety of genetic factors. Etiologic determinants and molecular pathophysiology of obesity have not yet understood clearly. Previously shown that genetic markers have a significant role in the development of obesity, although results are divergent with populations. Turkish Cypriots have a unique mixture of allele distributions as being a small-islander population. Therefore, the current study was aimed to evaluate the association between obesity and three putative obesity-related ADIPOQ, FTO and ACE gene markers, respectively. We investigated a possible association of ADIPOQ rs2241766 G>T, FTO rs9939609 A>T and ACE rs4340288 DIP variants among obese and non-obese Turkish Cypriot origin. Additionally, the correlation between these variants and biochemical and physical measurements were also evaluated to determine the possible biomarker for obesity in the population. Only FTO rs9939609 A>T polymorphism was associated with obesity and no association was observed with ADIPOQ rs2441666 G>T and ACE rs4340288 DIP. To conclude, FTO rs9939609 A allele found to have strong association with obesity in the population of Turkish Cypriots.

4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-ß-D-glucopyranoside effect in liver regeneration.

Following an injury or resection, the mammalian liver has the capacity to regain its former volume and functioning by restoring itself. Studies have demonstrated that antioxidants play a role in hepatic regeneration. This study investigated the effect of 4-(3,4-dihydroxybenzoyloxymethyl) phenyl-O-ß-D-glucopyranoside (PG) obtained from Origanum micranthum on liver regeneration. Sixty Wistar Albino rats were used. In the sham-operated group, a midline abdominal laparotomy was performed without hepatectomy. In the partial hepatectomy (PHx) group, the median and left lateral lobes were removed. Rats in the PHx group received 20 mg/kg/day PG intraperitoneally before being sacrificed at 24, 48, and 72 hrs, and 7 days later. Liver tissues were collected for immunohistochemical analysis and electron microscopic evaluation. We found an increase in mitotic index, and the numbers of Ki-67 stained hepatocytes in all PHx early stage groups (24 hr, 48hr, 72 hr), but not in 7-day groups. The regeneration mediators eNOS, iNOS, TNF-α and NF-κB were shown to increase in PHx groups. This increase was more prominent dependening on time. In the PHx treatment (PHx+PG) groups, while eNOS was still high, iNOS, TNF-α and NF-κB had decreased. The apoptotic index was markedly high in the PHx groups; this was prevented by PG treatment. These findings were supported by the ultrastructural results. Our findings indicate that PG supports liver regeneration, hepatocyte proliferation, reduced liver damage, and inflammatory mediators following PHx.

Does ureteral access sheat usage lead to permanent damage in the ureter? A placebo controlled trial in a rabbit model.

PURPOSE: To evaluate the clinical stenosis or precursor histological changes that ureteral access sheaths commonly used in ureteroscopic surgeries may cause in the long term in ureter. METHODS: In this study, the animals were divided into 9 groups and according to their groups, ureters of the rabbits were endoscopically fitted with 2F and 3F ureter catheters. The catheters were left in place and withdrawn after a specified period of time. All the ureters were excised and evaluated macroscopically, microscopically and histologically. Ureter diameters were measured and FGF-2 (+) labeled fibroblasts were counted in connective tissue as stenosis precursors. RESULTS: Macroscopically or microscopically, no stenosis was found in any group. The ureter diameter of the group that were catheterized for the longest time with the catheter that had the widest diameter was significantly lower than the group with the shorter duration and the catheter with the narrower diameter and the control group. When the groups were compared in terms of their FGF values, there was a significant difference in FGF-2 counts at all three ureter levels (p <0.05). CONCLUSION: The use of ureteral access sheath may lead to histological changes, as its diameter and duration increase.

Does ureteral access sheat usage lead to permanent damage in the ureter? A placebo controlled trial in a rabbit model

Abstract Purpose: To evaluate the clinical stenosis or precursor histological changes that ureteral access sheaths commonly used in ureteroscopic surgeries may cause in the long term in ureter. Methods: In this study, the animals were divided into 9 groups and according to their groups, ureters of the rabbits were endoscopically fitted with 2F and 3F ureter catheters. The catheters were left in place and withdrawn after a specified period of time. All the ureters were excised and evaluated macroscopically, microscopically and histologically. Ureter diameters were measured and FGF-2 (+) labeled fibroblasts were counted in connective tissue as stenosis precursors. Results: Macroscopically or microscopically, no stenosis was found in any group. The ureter diameter of the group that were catheterized for the longest time with the catheter that had the widest diameter was significantly lower than the group with the shorter duration and the catheter with the narrower diameter and the control group. When the groups were compared in terms of their FGF values, there was a significant difference in FGF-2 counts at all three ureter levels (p <0.05). Conclusion: The use of ureteral access sheath may lead to histological changes, as its diameter and duration increase.

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats.

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats. Rats were intraperitoneally administered saline, GTN (10 mg/kg), vehicle, saline + GTN, SC (50 µg/kg) + GTN, and SC alone. Also, ex vivo meningeal preparations were applied topically 100 µmol/L GTN, 50 µmol/L SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma, trigeminal neurons and superfusates were measured using enzyme-immunoassays. Dural mast cells were stained with toluidine blue. c-fos neuronal activity in trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical staining. The results showed that GTN triggered the increase in CGRP levels in plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise, GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural mast cell degranulation, but similar effects were not seen in ex vivo experiments. Salmon calcitonin administration ameliorated GTN-induced migraine pain by reversing the increases induced by GTN. Our findings suggested that salmon calcitonin could alleviate the migraine-like pain by modulating CGRP release at different levels including the generation and conduction sites of migraine pain and mast cell behaviour in the dura mater. Therefore salmon calcitonin may be a new therapeutic choice in migraine pain relief.

The effect of rhododendron honey on mice liver tissue / Efecto de la miel de rododendro en el tejido hepático de ratón

Rhododendron honey, made by bees from rhododendron pollen, contains a toxic substance called grayanotoxin. Depending on the dose, the poisonous honey can result in serious effects such as cardiac arrhythmia, fibrillation, and myocardial infarction. The purpose of this study is to investigate the effects of the poisonous RH of the Black Sea Region on the liver. Male mice were divided into five groups of twelve mice each, two being the control groups (distilled water) and the others being the rhododendron honey (RH) groups (25, 50, and 75 mg/kg) and 0.01 mg/kg grayanotoxin (GTx) groups. Liver tissues were collected 24 and 48 h later. The sections were stained with hematoxylin, eosin and PAS, then the histopathological score was performed. Significant statistical differences were observed between the RH and control groups in terms of congestion, steatosis, sinusoid dilatation, and inflammation. The control group demonstrated a normal liver structure in the light microscopy, while the GTx-applied 24 h group exhibited expansions in the sinusoids and congestion. Higher levels of congestion, steatosis, and inflammatory cells were seen in the GTx-applied 48 h group. In the same group, giant cells consisting of many nuclei were observed in the sinusoids. The results of the 25 mg RH-applied groups were similar in 24 and 48 h, histopathological score levels were increased slightly, congestion and steatosis were prominent in the 48 h group. Dense steatosis was seen in the hepatocytes around the vena centralis in 50 mg/kg RH-applied 48 h group. Congestion, steatosis and an increase in inflammatory cells were observed in the hepatocytes in the 75 mg/kg RH-applied 24- and 48 h groups. PAS (+) stained hepatocytes were decreased in the RH- and GTx-applied groups. The toxic effects of the rhododendron honey were observed in the mice liver tissue with respect to dose and time.

La miel de rododendro, elaborada por las abejas a partir del polen de rododendro, contiene una sustancia tóxica llamada grayanotoxina. Dependiendo de la dosis, la miel venenosa puede resultar en efectos graves, tales como arritmia cardiaca, fibrilación e infarto de miocardio. El propósito de este estudio fue investigar los efectos en el hígado de la miel venenosa de rododendro de la región del Mar Negro. Se distribuyeron ratones machos en cinco grupos de doce ratones cada uno, dos grupos control (agua destilada) y los otros grupos se trataron con la miel de rododendro (MR) (25, 50 y 75 mg/kg) y con 0,01 mg/kg grayanotoxina (GTX). Los tejidos hepáticos se recogieron 24 y 48 h más tarde. Las secciones fueron teñidas con hematoxilina-eosina y PAS. A continuación, se realizó la puntuación histopatológica. No se observaron diferencias estadísticamente significativas entre MR y los grupos de control en términos de congestión, esteatosis, dilatación sinusoidal e inflamación. El grupo control demostró una estructura normal del hígado en el microscopio de luz, mientras que el grupo de las 24 horas de aplicación de GTX exhibió expansiones en los sinusoides y congestión. Mayores niveles de congestión, esteatosis y células inflamatorias se observaron en el grupo de 48-horas de aplicación de GTX. En el mismo grupo, se observaron células gigantes que consistían en la presencia de muchos núcleos en los sinusoides. Los resultados de los grupos con aplicación de 25 mg de RH fueron similares en los resultados de 24 y 48 h, los niveles de puntuación histopatológica aumentaron ligeramente, la congestión y la esteatosis fueron prominentes en el grupo de 48 h. Se observó esteatosis densa en los hepatocitos en toda la vena central en el grupo de aplicación de 50 mg/kg de RH, 48 h. La congestión, la esteatosis y un aumento en las células inflamatorias se observaron en los hepatocitos en el grupo de 75 mg/kg de MR de 24 h y los grupos de 48 h. Hepatocitos teñidos con PAS (+) disminuyeron en los grupos de GTX y MR. Se observaron los efectos tóxicos de la miel de rododendro en el tejido hepático de ratones con respecto a la dosis y el tiempo.