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The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Dietrich F, Pietrobon Martins J, Kaiser S, Madeira Silva RB, Rockenbach L, Albano Edelweiss MI, Ortega GG, Morrone FB, Campos MM, Battastini AM - PLoS ONE (2015)

Bottom Line: Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions.Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder.This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.

ABSTRACT
Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

No MeSH data available.


Related in: MedlinePlus

Effect of treatment with Mesna or QAPF from Uncaria tomentosa on macroscopic evaluation of the bladder.The (A) hemorrhage, (B) edema, and (C) wet bladder weight was evaluated in CYP-induced hemorrhagic cystitis in mice. In graphics A–C, each column represents the mean of 12–13 animals, except for +QAPF 20 mg/kg, in which five animals were used. The vertical lines show the SEM. ###p<0.001 denotes the significance levels compared to saline values; *p<0.05; ***p<0.001 denotes the significance levels compared to CYP values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
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pone.0131882.g003: Effect of treatment with Mesna or QAPF from Uncaria tomentosa on macroscopic evaluation of the bladder.The (A) hemorrhage, (B) edema, and (C) wet bladder weight was evaluated in CYP-induced hemorrhagic cystitis in mice. In graphics A–C, each column represents the mean of 12–13 animals, except for +QAPF 20 mg/kg, in which five animals were used. The vertical lines show the SEM. ###p<0.001 denotes the significance levels compared to saline values; *p<0.05; ***p<0.001 denotes the significance levels compared to CYP values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.

Mentions: As shown in Fig 3, the i.p. administration of CYP (300 mg/kg) resulted in serious bladder damage, including severe hemorrhage and edema when compared to the saline group, as previously shown [21, 26]. According to the macroscopic evaluation of the bladder, the reference compound Mesna (60 mg/kg) caused a significant inhibition of the hemorrhage (Fig 3A) and of the edema (Fig 3B) induced by CYP. Treatment with QAPF was also able to markedly inhibit the formation of hemorrhage and edema after CYP application (Fig 3A and 3B, respectively).


The Quinovic Acid Glycosides Purified Fraction from Uncaria tomentosa Protects against Hemorrhagic Cystitis Induced by Cyclophosphamide in Mice.

Dietrich F, Pietrobon Martins J, Kaiser S, Madeira Silva RB, Rockenbach L, Albano Edelweiss MI, Ortega GG, Morrone FB, Campos MM, Battastini AM - PLoS ONE (2015)

Effect of treatment with Mesna or QAPF from Uncaria tomentosa on macroscopic evaluation of the bladder.The (A) hemorrhage, (B) edema, and (C) wet bladder weight was evaluated in CYP-induced hemorrhagic cystitis in mice. In graphics A–C, each column represents the mean of 12–13 animals, except for +QAPF 20 mg/kg, in which five animals were used. The vertical lines show the SEM. ###p<0.001 denotes the significance levels compared to saline values; *p<0.05; ***p<0.001 denotes the significance levels compared to CYP values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496084&req=5

pone.0131882.g003: Effect of treatment with Mesna or QAPF from Uncaria tomentosa on macroscopic evaluation of the bladder.The (A) hemorrhage, (B) edema, and (C) wet bladder weight was evaluated in CYP-induced hemorrhagic cystitis in mice. In graphics A–C, each column represents the mean of 12–13 animals, except for +QAPF 20 mg/kg, in which five animals were used. The vertical lines show the SEM. ###p<0.001 denotes the significance levels compared to saline values; *p<0.05; ***p<0.001 denotes the significance levels compared to CYP values. +Mesna represents CYP+Mesna; +QAPF represents CYP+QAPF.
Mentions: As shown in Fig 3, the i.p. administration of CYP (300 mg/kg) resulted in serious bladder damage, including severe hemorrhage and edema when compared to the saline group, as previously shown [21, 26]. According to the macroscopic evaluation of the bladder, the reference compound Mesna (60 mg/kg) caused a significant inhibition of the hemorrhage (Fig 3A) and of the edema (Fig 3B) induced by CYP. Treatment with QAPF was also able to markedly inhibit the formation of hemorrhage and edema after CYP application (Fig 3A and 3B, respectively).

Bottom Line: Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions.Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder.This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy.

View Article: PubMed Central - PubMed

Affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, ICBS, UFRGS, Porto Alegre, RS, Brazil.

ABSTRACT
Uncaria tomentosa is widely used in folk medicine for the treatment of numerous diseases, such as urinary tract disease. Hemorrhagic cystitis (HE) is an inflammatory condition of the bladder associated with the use of anticancer drugs such as cyclophosphamide (CYP). Sodium 2-mercaptoethanesulfonate (Mesna) has been used to prevent the occurrence of HE, although this compound is not effective in established lesions. It has been demonstrated that the purinergic system is involved in several pathophysiological events. Among purinergic receptors, P2X7 deserves attention because it is involved in HE induced by CYP and, therefore, can be considered a therapeutic target. The objective of this study was to investigate the potential therapeutic effect of the quinovic acid glycosides purified fraction (QAPF) from U. tomentosa in the mouse model of CYP-induced HE. Pretreatment with QAPF not only had a protective effect on HE-induced urothelial damage (edema, hemorrhage and bladder wet weight) but was also able to control visceral pain, decrease IL-1β levels and down-regulates P2X7 receptors, most likely by inhibit the neutrophils migration to the bladder. This research clearly demonstrates the promising anti-inflammatory properties of QAPF, supporting its use as complementary therapy. QAPF represents a promising therapeutic option for this pathological condition.

No MeSH data available.


Related in: MedlinePlus