RESUMO
This study aimed to assess the ability of rosmarinic acid (RA) to prevent kidney stone formation in an ethylene glycol and ammonium chloride (EG/AC) model. There was an increase in diuresis in the normotensive (NTRs) and hypertensive rats (SHRs) treated with hydrochlorothiazide (HCTZ) and exposed to EG/AC, while RA restored urine volume in NTRs. The EG/AC groups exhibited lower urine pH and electrolyte imbalance; these parameters were not affected by any of the treatments. Both HCTZ+EG/AC and RA+EG/AC reduced calcium oxalate crystal formation in NTR and SHR urine. Kidney tissue analysis revealed alterations in oxidative stress and inflammation parameters in all EG/AC-receiving groups, with RA enhancing antioxidant defenses in SHRs. Additionally, crystals were found in the kidney histology of all EG/AC-exposed groups, with reduced Bowman's capsule areas in NTRs and SHRs. The NTR VEH+EG/AC group showed intense renal damage, while the others maintained their structures, where treatments with HCTZ and RA were fundamental for kidney protection in the NTRs. Docking analysis showed that RA exhibited good binding affinity with matrix metalloproteinase-9, phosphoethanolamine cytidylyltransferase, and human glycolate oxidase enzymes. The data disclosed herein underscore the importance of further research to understand the underlying mechanisms better and validate the potential of RA for clinical use.
RESUMO
This research demonstrates the diuretic effect of naringenin, a flavanone aglycone found in citrus, on spontaneously hypertensive female and male rats (SHR). The data reinforces existing literature findings that male SHR exhibits higher systolic blood pressure than age-matched females. Urine volume assessed over 8â hours was lower when obtained from SHR males than females. When these animals were orally treated with different doses of naringenin (0.1-1â mg/kg), this increased urinary volume in both genders at the highest dose tested. In contrast, the lowest dose promoted a significant natriuretic effect. The other electrolytes analyzed in urine were not significantly altered, except potassium excretion, which was shown to be increased in the urine of SHR males. Furthermore, naringenin showed promise in reducing calcium oxalate (CaOx) crystal formation in an inâ vitro model, presenting potential advantages in lithiasis prevention.
Assuntos
Hipertensão , Urolitíase , Ratos , Feminino , Masculino , Animais , Ratos Endogâmicos SHR , Natriurese/fisiologia , Hipertensão/tratamento farmacológico , Hipertensão/prevenção & controle , Diurese/fisiologia , Urolitíase/tratamento farmacológico , Urolitíase/prevenção & controleRESUMO
BACKGROUND: Previous studies indicate the renal vasodilating effects of boldine, an alkaloid found in Peumus boldus. However, its potential to induce diuresis still needs to be studied. METHODS: Wistar rats were used and the urine volume was noted for 8 h and further studied. RESULTS: The acute treatment at 0.1 and 0.3 mg/kg of boldine showed a diuretic, natriuretic, and Ca2+-sparing effect in rats without changing the urinary elimination of K+and Cl-. When boldine was given in combination with hydrochlorothiazide, there was an increase in urinary volume compared to the vehicle group. However, this was not different from the treatments in its isolated form. Urine Ca2+values ââremained low but were not enhanced by this association. The excretion of Na+and Cl- was significantly increased compared to the group that received only vehicle or boldine. On the other hand, although the association of amiloride plus boldine did not result in a diuretic effect, the increase in Na+and the reduction in K+excretion were significantly potentiated. Furthermore, in the presence of the non-selective muscarinic receptor antagonist atropine, boldine showed reduced capacity to increase urinary volume, maintaining the natriuretic and Ca2+-sparing effect, besides a very evident K+-sparing action. Similar results were obtained in the presence of the non-selective cyclooxygenase inhibitor indomethacin. Furthermore, boldine showed an ex vivo antiurolithiasis activity, reducing calcium oxalate's precipitation and crystallization. CONCLUSIONS: This study reveals the diuretic, natriuretic, Ca2+-sparing, and antiurolithiatic effects of boldine, an action possibly related to muscarinic receptor activation and prostanoid generation.
Assuntos
Aporfinas , Diuréticos , Ratos , Animais , Diuréticos/farmacologia , Cálcio , Ratos Wistar , Aporfinas/farmacologia , Sódio , Receptores MuscarínicosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tagetes erecta L., known as marigold, belongs to the Asteraceae family and is mainly found in South America. Despite reports that T. erecta flowers are used in folk medicine to treat cardiovascular and renal diseases, there is no study regarding its diuretic effect. AIM: This study aimed to evaluate the chemical composition and the diuretic efficacy of the hydroethanolic extract from T. erecta (HETE) in normotensive (NTR) and hypertensive (SHR) rats. MATERIAL AND METHODS: The HETE was analyzed by liquid chromatography coupled to diode array detector and mass spectrometry (LC-DAD-MS). Female and male NTR and SHR received the treatment with vehicle, HETE (0.01 mg/kg, 0.1 mg/kg, and 1 mg/kg) or hydrochlorothiazide (HCTZ; 5 mg/kg) orally. The urinary parameters were measured at the end of the 8-h experiment. RESULTS: From HETE, saccharides and triterpenes were the main annotated compounds, such as erythrodiol and ß-amyrin. The urine volume was significantly increased in the groups treated with HETE, in both male and female NTR and SHR rats, compared to the respective vehicle-treated groups. Regarding electrolytes elimination, the treatment with HETE did not reveal significant changes in the urine levels of K+ or Cl-, but it showed a natriuretic and Ca2+-sparing effects. The HETE beneficial result in reducing Ca2+ excretion was confirmed through the protective effect found in front of the urinary calcium oxalate precipitation and crystallization. The combination with HCTZ, a classic diuretic and saluretic medicine, significantly enhanced HETE-induced diuresis, natriuresis, and the Ca2+-sparing effect. On the other hand, the K+-sparing action was improved in the combination of HETE with amiloride, a standard K+-sparing diuretic. In contrast, the combination of HETE with atropine (a non-selective muscarinic receptor antagonist) and indomethacin (an inhibitor of the cyclooxygenase enzyme), promoted an important reduction in urinary volume, but interestingly the natriuretic effect was maintained. CONCLUSION: This study contributed to the preclinical validation of the diuretic efficacy of T. erecta, highlighting this species as promising for the development of new pharmacological strategies for the management of kidney disorders.