Kynurenine Pathway Dysregulation and Pain Perception in Acute Pancreatitis: Has the Connection Unraveled?

AIM: Tryptophan (TRP), an essential amino acid, undergoes catabolism through various pathways. Notably, the kynurenine pathway (KP), constituting one of these pathways, exhibits a unidirectional impact on immune response and energy metabolism. Nonetheless, its influence on pain sensation is characterized by biphasic dynamics. This study aims to scrutinize the influence of the KP pathway on pain sensation, particularly within the context of pancreatic inflammation. METHODS: Our prospective case-control study involved individuals diagnosed with acute pancreatitis and a control group matched for gender and age. The patient cohort was subsequently subdivided into severe and non-severe subgroups. To assess metabolites within KP, two blood samples were collected from the patient cohort, one at the time of diagnosis and another during the recovery phase. Furthermore, for pain quantification, daily pain scores utilizing the Visual Analog Scale (VAS) were extracted from the patients' medical records. RESULTS: The study incorporated 30 patients along with an equivalent number of controls. A noticeable distinction was evident between the patient and control groups, characterized by an increase in kynurenine levels and a decrease in the tryptophan/kynurenine ratio. Throughout the process of disease recovery, a uniform decrease was observed in all KP metabolites, excluding 3-Hydroxykynurenine. Elevated levels of Kynurenic acid (KYNA) were correlated with increased pain scores. Critically, no apparent distinctions in KP metabolites were discerned concerning pain severity in patients with comorbidities characterized by neural involvement. CONCLUSION: Based on our results, the kynurenine pathway (KP) is activated in instances of acute pancreatitis. Elevated levels of KYNA were found to be associated with heightened pain scores. The operative stages within the KP responsible for pain modulation are impaired in cases characterized by neuropathy-induced pain sensation.

Can magnesium sulfate prophylaxis reduce colistin nephrotoxicity? / ¿Puede la profilaxis con sulfato de magnesio reducir la nefrotoxicidad de la colistina?

The study aimed to investigate the role of magnesium sulfate prophylaxis in nephrotoxicity caused by colistin. Thirty Wistar Albino rats were divided into four groups: control, colistin, magnesium (Mg), and Mg+colistin. The drugs were administered to the groups for seven days. Urea-creatinine values were measured at the beginning (T0) and end (T1) of the study. Malondialdehyde (MDA) levels were measured in plasma and kidney tissue, glutathione (GSH) levels were analyzed in the erythrocyte and kidney tissues. At the end of the study, the semiquantitative score (SQS) was calculated by the histopathological examination of the kidneys. Urea values significantly decreased in Mg and Mg+colistin groups compared to the baseline (p=0.013 and p=0.001). At the time of T1, these groups had significantly lower urea values than the colistin and control groups. Creatinine value was significantly increased in the colistin group compared to baseline (p=0.005), the creatinine value in the colistin group was significantly higher than the Mg+colistin group (p=0.011). Plasma MDA levels were significantly higher in the colistin group compared to the other groups at the time of T1 (p<0.001). The Mg+colistin group had lower renal MDA levels than the colistin group. The colistin group had significantly higher renal tubular grade (p=0.035), renal affected area (p<0.001), and SQS (p=0.001) than the Mg+colistin group. The results of the study suggested that Mg sulfate may have a nephrotoxicity-reducing effect on colistin. (AU)

El objetivo del estudio fue investigar la función de la profilaxis con sulfato de magnesio en la nefrotoxicidad causada por la colistina. Se dividieron 30 ratas Wistar albinas en 4 grupos: control, colistina, magnesio (Mg) y Mg + colistina. Los fármacos se administraron a los grupos durante 7 días. Los valores de urea-creatinina se midieron al principio (T0) y al final (T1) del estudio. Se midieron los niveles de malondialdehído (MDA) en el plasma y el tejido renal, y se analizaron los niveles de glutatión (GSH) en los eritrocitos y el tejido renal. Al final del estudio, se calculó la puntuación semicuantitativa (semiquantitative score [SQS]) mediante el examen histopatológico de los riñones. Los valores de urea disminuyeron significativamente en los grupos de Mg y Mg + colistina en comparación con los valores iniciales (p = 0,013 y p = 0,001). En el momento del T1, estos grupos tenían valores de urea significativamente más bajos que los grupos de colistina y de control. El valor de creatinina se incrementó significativamente en el grupo de colistina en comparación con el valor inicial (p = 0,005); el valor de creatinina en el grupo de colistina fue significativamente mayor que en el grupo de Mg + colistina (p = 0,011). Los niveles de MDA en el plasma fueron significativamente más altos en el grupo de colistina en comparación con los otros grupos en el momento del T1 (p < 0,001). El grupo de Mg + colistina presentó niveles renales de MDA más bajos que el grupo de colistina. El grupo de colistina presentó un grado tubular renal (p = 0,035), un área renal afectada (p < 0,001) y una SQS (p = 0,001) significativamente mayores que el grupo de Mg + colistina. Los resultados del estudio indicaron que el sulfato de Mg puede tener un efecto reductor de la nefrotoxicidad de la colistina. (AU)