Fig 1.
Acute docetaxel treatment increases time to recovery from shock-induced seizure-like behaviors with increasing concentration in C. elegans.
(A) Acute exposure to docetaxel increases time to recovery in a concentration-dependent manner. Different letters denote a statistically significant difference in the mean values between the groups, where “a” stands for not statistically significantly different from M9 saline and “b” stands for statistically significantly different from M9 saline (Student-Newman Keuls, p < 0.05). Data shown as mean ± s.e.m. (B) Acute exposure to increasing concentrations of docetaxel increases the percentage of non-recovered worms following the electroshock. 0.001 mM DTX vs. M9, X2 = 16.6071, p < 0.0001; 0.002 mM DTX vs. M9, X2 = 18.7615, p < 0.0001; 0.0035 mM DTX vs. M9, X2 = 19.3063, p < 0.0001; 0.005 mM DTX vs. M9, X2 = 21.698, p < 0.0001; 0.01 mM DTX vs. M9, X2 = 20.7299, p < 0.0001; 1 mM DTX vs. M9, X2 = 24.2858, p < 0.0001. N > 30 for each group. ****, p < 0.0001, compared to M9.
Fig 2.
Nematodes treated with chronic docetaxel, display an increase in time to recovery from shock-induced seizure-like behaviors when compared to nematodes exposed to M9 saline alone.
(A) Chronic exposure to docetaxel increases time to recovery with increasing concentrations. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, “b” stands for statistically significantly different from M9 saline, and “c” stands for statistically significantly different from M9 saline and solutions labeled “b” (Student-Newman Keuls, p < 0.05). Data shown as mean ± s.e.m. (B) Chronic exposure to increasing concentrations of docetaxel increases the percentage of non-recovered worms following the electroshock. C.E. 0.0035 mM DTX vs. M9, X2 = 11.9656, p = 0.0005; C.E. 0.005 mM DTX vs. M9, X2 = 8.4176, p = 0.0037; C.E. 1 mM DTX vs. M9, X2 = 24.7284, p < 0.0001. N > 30 for each group. The horizontal reference line (0.01 mM Docetaxel Acute Exposure) indicates the mean value observed for acute exposure to 0.01 mM docetaxel [Fig 1]. **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; all compared to M9.
Fig 3.
Acute treatment with sildenafil citrate decreases the duration of shock-induced seizure-like behaviors that accompany acute exposure to docetaxel.
(A) Acute treatment with sildenafil citrate significantly decreases time to recovery for worms acutely treated with 0.01 mM docetaxel. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, “b” stands for statistically significantly different from M9 saline, and “a/b” stands for not statistically significantly different from M9 saline or solutions labeled “b” (Student-Newman Keuls, p < 0.05). Data shown as mean ± s.e.m. (B) Acute treatment with sildenafil citrate decreases the percentage of non-recovered worms following the electroshock. 0.5 mM S.C. vs. M9, X2 = 2.9668, p = 0.0850; 0.01 mM DTX vs. M9, X2 = 25.0325, p < 0.0001; 0.01 mM DTX. vs. 0.06 mM S.C. + 0.01 mM DTX, X2 = 28.1521, p < 0.0001; 0.01 mM DTX vs. 0.125 mM S.C. + 0.01 mM DTX, X2 = 23. 4833, p < 0.0001; 0.01 mM DTX vs. 0.25 mM S.C. + 0.01mM DTX, X2 = 24.9289, p < 0.0001; 0.01 mM DTX vs. 0.5 mM S.C. + 0.01 mM DTX, X2 = 29.0098, p < 0.0001; 0.01 mM DTX vs. 1 mM S.C. + 0.01 mM DTX, X2 = 18.9077, p < 0.0001. N > 30 for each group. ****, p < 0.0001, compared to M9. ####, p < 0.0001, compared to 0.01 mM DTX. S.C., Sildenafil Citrate; DTX, Docetaxel.
Fig 4.
Acute treatment with RVM-3 decreases the duration of shock-induced seizure-like behaviors that accompany acute exposure to docetaxel.
(A) Acute treatment with RVM-3 significantly decreased time to recovery for worms treated with 0.01 and 1 mM docetaxel. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, and “b” stands for statistically significantly different from M9 saline (Student-Newman Keuls, p < 0.05). Data shown as mean ± s.e.m. (B) Acute treatment with 100 µM RVM-3 significantly decreases the percentage of non-recovered worms treated with 1 mM docetaxel. 100 µM RVM3 vs. M9, X2 = 0.3233, p = 0.5696; 0.01 mM DTX vs. M9, X2 = 13.1767, p < 0.0001; 1 mM DTX vs. M9, X2 = 38.3749, p < 0.0001; 0.01 mM DTX vs. 0.01 mM DTX + 100 µM RVM3, X2 = 1.5921, p = 0.2070; 1 mM DTX vs. 1 mM DTX + 100 µM RVM3, X2 = 12.2982, p < 0.0005. N > 30 for each group. ***, p < 0.001; ****, p < 0.0001; all compared to M9. ###, p < 0.001, compared to 1 mM DTX. RVM-3, Resveramorph 3.
Fig 5.
Acute treatment with sildenafil citrate decreases the duration of shock-induced seizure-like behaviors that accompany chronic exposure to docetaxel.
(A) Acute treatment with various concentrations of sildenafil citrate significantly decreases time to recovery for worms treated with chronic 0.005 mM docetaxel. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, and “b” stands for statistically significantly different from M9 saline (Student-Newman Keuls, P < 0.05). Data shown as mean ± s.e.m. (B) Acute treatment with 0.10 and 0.25 mM sildenafil citrate decreases percent non-recovery following electroshock of nematodes exposed to chronic 0.005 mM docetaxel, while higher concentrations (0.5 and 1 mM) were less effective. 0.5 mM S.C. vs. M9, X2 = 0.0248, p = 0.8749; 0.005 mM DTX vs. M9, X2 = 5.1534, p = 0.0232; C.E. 0.005 mM DT vs.0.1 mM S.C. + C.E. 0.005 mM DTX, X2 = 5.3657, p = 0.0205; C.E. 0.005 mM DTX vs. 0.25 mM S.C. + C.E. 0.005 mM DTX, X2 = 9.6243, p = 0.0019; C.E. 0.005 mM DTX vs. 0.5 mM S.C. + C.E. 0.005 mM DTX, X2 = 1.6623, p = 0.1973; C.E. 0.005 mM DTX vs. 1 mM S.C. + C.E. 0.005 mM DTX, X2 = 2.756, p = 0.0969. N > 30 for each group. *, p < 0.05, compared to M9. #, p < 0.05; ###, p < 0.001; all compared to 0.005 mM C.E. DTX. S.C., Sildenafil Citrate.
Fig 6.
Acute treatment with RVM 3 decreases the duration of shock-induced seizure-like behaviors that accompany chronic exposure to docetaxel.
(A) Acute treatment with RVM 3 significantly decreases time to recovery for worms treated with chronic 0.005 mM docetaxel. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, and “b” stands for statistically significantly different from M9 saline (Student-Newman Keuls, P < 0.05). Data shown as mean ± s.e.m. (B) Acute treatment with RVM 3 does not decrease the percentage of non-recovered worms subjected to chronic 0.005 mM docetaxel exposure. 100 µM RVM3 vs. M9, X2 = 0.1079, p = 0.7425; C.E. 0.005 mM DTX vs. M9, X2 = 3.6308, p = 0.0567; C.E. 0.005mM DTX vs. 100 µM RVM3 + C.E. 0.005 mM DTX, X2 = 0.0021, p = 0.9634. *, p < 0.05, compared to M9. RVM-3, Resveramorph 3; C.E DTX, chronic exposure to 0.005 mM docetaxel.
Fig 7.
Acute treatment with RVM-3 decreases the duration of shock-induced seizure-like behaviors associated with acute and chronic exposure to docetaxel.
(A) Acute treatment with RVM-3 significantly decreased time to recovery in worms treated with acute and/or chronic 0.0035 and 0.01 mM docetaxel. Different letters denote a statistically significant difference in the mean values between the groups where “a” stands for not statistically significantly different from M9 saline, “b” stands for statistically significantly different from M9 saline, “c” stands for statistically significantly different from M9 saline and other labeled solutions, and “d” stands for statistically significantly different form M9 saline and other labeled solutions (Student-Newman Keuls, P < 0.05). Data shown as mean ± s.e.m. (B) Acute treatment with RVM-3 decreased %NR in animals treated with chronic 0.0035 and 0.01 mM docetaxel, following the electroshock. 100 µM RVM3 vs. M9, X2 = 0.0888, p = 0.7657; Acute 0.0035 mM DTX vs. M9, X2 = 12.1153, p < 0.0001; C.E. 0.0035 mM DTX in M9 vs. M9, X2 = 9.7686, p = 0.0018; C.E. 0.0035 mM DTX in 0.0035 mM DTX vs. M9, X2 = 9.1983, p = 0.0024; C.E. 0.0035 mM DTX in 100 µM RVM3 vs. M9, X2 = 0.5822, p = 0.4455; Acute 0.01 mM DTX vs. M9, X2 = 10.4772, p = 0.0012; C.E. 0.01 mM DTX in M9 vs. M9, X2 = 10.3204, p = 0.0013; C.E. 0.01 mM DTX in 0.01 mM DTX vs. M9, X2 = 12.8355, p < 0.0001; C.E. 0.01 mM DTX in 100 µM RVM3 vs. M9, X2 = 1.2115, p = 0.2710; C.E. 0.01 mM DTX in 0.01 mM DTX + 100 µM RVM3 vs. M9, X2 = 1.1258, p = 0.2887. N > 30 for each group. **, p < 0.01; ***, p < 0.001; ****, p < 0.0001; all compared to M9. RVM-3, Resveramorph 3; DTX, Docetaxel.