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Association between nonalcoholic fatty liver disease and severe male reproductive organ impairment (Germinal Epithelial Loss): Study on a mouse model and on human patients

URIEL ALEJANDRO LOPEZ LEMUS RAQUEL GARZA GUAJARDO ORALIA BARBOZA QUINTANA ALEJANDRINA RODRIGUEZ HERNANDEZ José Guzmán Esquivel ALEJANDRO GARCÍA RIVERA VIOLETA M. MADRIGAL PÉREZ LAURA ELVIRA GARCÍA LABASTIDA ALEJANDRO DAVID SORIANO HERNANDEZ MARGARITA DE LA LUZ MARTINEZ FIERRO IRAM PABLO RODRIGUEZ SANCHEZ ELIZABETH SANCHEZ DUARTE ARIANA CABRERA LICONA GABRIEL CEJA ESPIRITU IVAN DELGADO ENCISO (2018, [Artículo])

Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the thoracic aorta, liver tissue, and testicular tissue from the deceased subjects were collected. The degree of germinal epithelial loss (DGEL) was evaluated and the clinical and histologic data were compared between individuals with and without NAFLD. The only metabolic or morphologic variable that caused a significant difference in the DGEL, in both the animal model and humans, was the presence of liver steatosis. The percentage of steatosis was also correlated with the percentage of the DGEL. In humans, steatosis (greater than 20%) increased the risk 12-fold for presenting with a severe DGEL (OR: 12.5; 95% CI [1.2, 128.9]; p = .03). There was no association with age above 50 years or MS components. Steatosis grade was also correlated with atherosclerosis grade. NAFLD was a strongly associated factor implicated in severe DGEL, as well as the testis was identified as a probable target organ for damage caused by the disease. his finding could result in the search for new approach strategies in the management of men with fertility problems. Further studies are required to confirm these results.

MEDICINA Y CIENCIAS DE LA SALUD Germ cells Atherosclerosis Testis Metabolic syndrome

Hacia el desarrollo de un nuevo antiparasitario basado en células en suspensión de Carica papaya

CYNTHIA ALEJANDRA GUZMÁN MEDINA (2023, [Tesis de doctorado])

Las enfermedades parasitarias son un problema de salud pública que afectan a más de la

quinta parte de la población a nivel mundial. Además de la morbilidad que generan, sino

son tratadas y controladas de manera adecuada pueden llegar a causar la muerte.

En el mercado existen diferentes antiparasitarios comerciales, que si bien son efectivos,

presentan diferentes efectos adversos tanto para el individuo parasitado (i.e. destrucción

de la microbiota intestinal) como para el medio ambiente. Este panorama señala la

relevancia de desarrollar tratamientos antiparasitarios más amigables con el ambiente y con

menores efectos adversos que estén disponibles actualmente en el mercado. Productos

obtenidos a partir de plantas con propiedades anti-parasitarias, cultivadas in vitro en

condiciones controladas, podrían representar una alternativa realista. Entre ellas figura la

planta Carica papaya, especie de zonas tropicales y subtropicales del planeta a cuyos frutos

se les adjudica actividades antiparasitarias. Estas propiedades se atribuyen a algunos de

sus compuestos concentrados en el latex y en las semillas como la papaina, la

quimiopapaína, la lisozima, la glicil-endopeptidasa, la proteasa de cisteína y el benzil-

isotiocinato.

El objetivo del presente trabajo fue evaluar la actividad antiparasitaria in vitro e in vivo de

un conjunto de callos y líneas de células de papaya de Carica papaya contra cisticercos de

Taenia crassiceps (cestodo) y contra trofozoitos de Entamoeba histolytica (protozoario). Los

extractos acuosos obtenidos a partir de callos y células cultivados en placa o en suspensión,

respectivamente, de las diferentes líneas de papaya revelaron alta capacidad cisticida

(>98% de mortalidad) in vitro contra cisticercos de Taenia crassiceps. En la evaluación in

vivo la línea no transformada obtuvo mayor efecto cisticida a 10mg/mL reduciendo el

número de cisticercos gemantes y aumentando los cisticercos calcificados en niveles

similares a los obtenidos utilizando antiparasitarios comerciales (albendazol y niclosamida).

Las líneas transformadas y sin transformar de papaya evaluadas indujeron una alta

capacidad amebicida (97% de mortalidad) in vitro contra trofozoitos de Entamoeba

histolytica. Las diferentes líneas transformadas y sin transformar de papaya redujeron

significativamente el número de abscesos amebianos y previnieron la hepatomegalia de

manera no significativamente diferente que el anti-parasitario comercial (metronidazol).

Los resultados generados en el presente estudio señalan al extracto acuoso obtenido a

partir de cultivos en suspensión de células de papaya transformada y no transformada

indujeron alto nivel de protección in vitro e in vivo por lo tanto; este es un producto efectivo

para el tratamiento de la cisticercosis y la amebiasis.

Parasitic diseases are a public health problem that affect more than a fifth of the population

worldwide. Additionally, and along with the morbidity the produce, they can cause death if

they are not treated and controlled adequately.

There are different commercial antiparasitic on the market which, although effective,

present different adverse effects both for the individual (i.e., destruction of the intestinal

microbiota) and for the environment alike. This panorama points out the relevance of

developing more environmentally friendly antiparasitic treatments with fewer adverse effects

than the ones currently available on the market. Products obtained from plants with anti-

parasitic properties, grown in vitro under controlled conditions, could represent a realistic

alternative. Among them is the Carica papaya, a species from tropical and subtropical areas

of the planet whose fruits are believed to have antiparasitic activities. These properties are attributed to some of its compounds concentrated in the latex and seeds such as papain,

chymopapain, lysozyme, glycyl-endopeptidase, cysteine-proteinase and benzyl-

isothiocyanate.

The objective of the present work is to evaluate the in vitro and in vivo antiparasitic activity

of a set of papaya callus and cell lines from Carica papaya against cysticerci of Taenia

crassiceps (cestode) and against trophozoites of Entamoeba histolytica (protozoan). The

aqueous extracts obtained from callus and cells cultured in plates or in suspension,

respectively, of the different papaya lines revealed high cysticidal capacity (>98% mortality)

in vitro against Taenia crassiceps cysticerci. Meanwhile, in the in vivo evaluation, the non-

transformed line obtained a greater cysticidal effect at 10 mg/mL, reducing the number of

budding cysticerci and increasing calcified cysticerci at levels like those obtained using

commercial antiparasitic (albendazole and niclosamide). The papaya lines evaluated

induced a high amoebicidal capacity (97% mortality) in vitro against Entamoeba histolytica

trophozoites. The different papaya lines significantly reduced the number of amoebic

abscesses and prevented hepatomegaly in a non-significantly different manner than the

commercial anti-parasitic (metronidazole).

The results produced in this thesis indicate that the aqueous extract obtained from

suspension cultures of transformed and non-transformed papaya cells induced a high level

of protection in vitro and in vivo. Therefore, this may represent an effective product for the

treatment of cysticercosis and amoebiasis.

CIENCIAS AGROPECUARIAS Y BIOTECNOLOGÍA CIENCIAS AGRARIAS Carica papaya, antiparasitario, células en suspensión, T. crassiceps, E. histolytica. Carica papaya, antiparasitic, in-suspension cells, T. crassiceps, E. histolytica.