The protection afforded by kefir against cyclophosphamide induced testicular toxicity in rats by oxidant antioxidant and histopathological evaluations.

Cyclophosphamide (CTX) is the most commonly used effective alkylating drug in cancer treatment, but its use is restricted because its toxic side effect causes testicular toxicity. CTX disrupts the tissue redox and antioxidant balance and the resulting tissue damage causes oxidative stress. In our study based on this problem, kefir against CTX-induced oxidative stress and testicular toxicity were investigated. Rats were divided into 6 groups: control, 150 mg/kg CTX, 5 and 10 mg/kg kefir, 5 and 10 mg/kg kefir + 150 CTX. While the fermented kefirs were mixed and given to the rats for 12 days, CTX was given as a single dose on the 12th day of the experiment. Testis was scored according to spermatid density, giant cell formation, cells shed into tubules, maturation disorder, and atrophy. According to our biochemical findings, the high levels of total oxidant status (TOS), and the low levels of total antioxidant status (TAS) in the CTX group, which are oxidative stress markers, indicate the toxic effect of CTX, while the decrease in TOS levels and the increase in TAS levels in the kefir groups indicate the protective effect of kefir. In the CTX-administered group, tubules with impaired maturation and no spermatids were observed in the transverse section of the testicle, while in the kefir groups, the presence of near-normal tubule structures and tubule lumens despite CTX showed the protective effect of kefir. In our study, it was observed that kefir had a protective and curative effect on CTX-induced toxicity and oxidative stress and could be a strong protector.

Neuroprotective effects of daidzein against ifosfamide-induced neurotoxicity in male rats: role of selected inflammatory and apoptotic markers.

Ifosfamide (IFO), an alkylating chemotherapy agent, is known for its association with neurotoxicity and encephalopathy. This trial was designed to evaluate the protective action of daidzein (DZN) against IFO-induced neurotoxicity in male rats by determining the difference in certain inflammatory and apoptotic markers in the brain tissue of rats. Twenty-eight Wistar rats, weighing 120-150 g, were divided into four groups of seven rats: Group 1 (Control) received no treatment; Group 2 was orally administered DZN (100 mg/kg/day) for seven days; Group 3 received a single intraperitoneal (IP) dose of IFO (500 mg/kg); Group 4 received oral DZN (100 mg/kg/day) for one week prior to a single IP dose of IFO on the seventh day. Twenty-four hours post-treatment, serum and brain tissue samples were collected for analysis. The results indicated a significant increase in serum inflammatory markers (TNF-alpha, IL-6, and iNOS) and the anti-inflammatory marker (IL-10), along with elevated caspase-3 enzyme activity in the brain tissue of the IFO-treated group compared to the control group. Conversely, pre-treatment with DZN significantly reduced serum inflammatory markers and caspase-3 levels in tissue. The findings suggest that daidzein has anti-inflammatory and anti-apoptotic properties, potentially offering protection against IFO-induced neurotoxicity in rats.

Quimioterápicos y cardiotoxicidad: un enfoque actual y práctico para el clínico de una disciplina en pleno desarrollo / Chemotherapy agents and cardiotoxicity: a current and user-friendly approach for the clinician, a developing discipline

La cardiotoxicidad por fármacos quimioterápicos es un efecto adverso frecuente y esperado. En este sentido se ha creado una especialización, la cardiooncología, que tiene como principal objetivo la prevención de estos efectos. La forma de expresión de este fenómeno es muy variada, pudiendo manifestarse como: insuficiencia cardíaca, hipertensión arterial, eventos coronarios agudos y/o trastornos del ritmo. La clave en la prevención está en la idividualización del riesgo cardiotóxico de cada paciente (en base a factores reconocidos como edad, sexo, irradiación mediastinal previa, tipo de fármaco, dosis acumulada, cardiopatía asociada previamente) y el riesgo potencial cardiotóxico de cada quimioterápico. En este sentido se han creado algoritmos de actuación fundamentados en la monitorización y el inicio de tratamiento precoz y oportuno de cada efecto, previniendo el mal mayor en cada paciente.

Fetal Central Nervous System and Thymic Alterations Following Cyclophosphamide Treatment of Pregnant Mice / Alteraciones del Sistema Nervioso Central Fetal y Tunicas Posterior al Tratamiento con Ciclofosfamida en Ratas Preñadas

The present study assessed central nervous system (CNS) and immune system changes in murine fetuses after cyclophosphamide (CP) exposure during intrauterine life. A single CP dose of 0, 10, or 20mg/kg body weight was administered by intraperitoneal inj ection to pregnant mice (20/group) on day 11 of gestation (GD 11) and fetuses were evaluated on day 19 of gestation (GD 19). Fetuses were examined for external changes, and then the brains and thymuses were removed for further evaluations of histological changes, protein content, apoptotic cell count, DNA fragmentation, and in vitro cell proliferation using 1 fetus/litter for each assessment. Brains and thymuses from CP-exposed fetuses were smaller in size and distorted in overall shape compared to those from the control group. Estimated mean protein content (mg/mL) of brains was decreased in the CP-exposed groups. In both brain cells and thymocytes there was an increase in mean apoptotic cell counts and in mean percent DNA fragmentation in the exposed groups. The in vitro cell proliferation assays conducted with cells from exposed fetuses exhibited a mean decrease in the number of both brain cells and thymocytes generated. These findings indicate that maternal CP treatment on GD 11 in mice results in marked fetal toxicity characterized by reduced live litter size, fetal body weights as well as brain and thymic weights and malformations which are accompanied by changes in brain protein content, brain and thymic apoptosis, DNA fragmentation and in vitro cell proliferation at term.

El presente estudio evaluó los cambios en el sistema nervioso e inmunológico en fetos de roedores, luego de exposición a ciclofosfamida (CF) durante la vida intrauterina. Una dosis única de CF de 0, 10, y 20 mg/kg de peso se administró por medio de inyección intraperitoneal en ratas preñadas (grupo de 20) en el día 11 de gestación (DG11) y luego los fetos se evaluaron en el día 19 de gestación (DG19). Fueron examinados los cambios externos de los fetos, y los cerebros y timos se extrajeron para evaluar los cambios histológicos, contenido de proteínas, conteo de células apoptóticas, fragmentación de DNA y proliferación de células in vitro, usando 1 feto por carnada para cada evaluación. Los cerebros y timos de fetos expuestos a CF eran pequeños y completamente deformados , comparado con los del grupo control. La estimación del contenido proteico (mg/mL) de los cerebros estuvo disminuida en los grupos expuestos a CF. En las células del cerebro y timocitos hubo un incremento en el promedio del conteo de células apoptóticas y el porcentaje promedio de la fragmentación de DNA en los grupos expuestos. Los ensayos de proliferación celular in vitro realizados en células de fetos expuestos, mostraron una disminución en el promedio de células cerebrales y timocitos generados. Estos hallazgos indican que el tratamiento materno en el DG11 con CF en ratones significa una marcada toxicidad fetal caracterizada por un reducido tamaño de los nacidos vivos de la carnada, reducidos pesos fetal, cerebral y del timo y malformaciones, las cuales son acompañadas por cambios en el contenido proteico cerebral, apoptosis de células cerebrales y del timo, fragmentación del DNA y proliferación celular in vitro al término.